PanelApp (staging)

Activity

Filter

Cancel
Date Panel Item Activity
3000 actions
BabyScreen+ newborn screening v1.116 CLN8 Melanie Marty reviewed gene: CLN8: Rating: GREEN; Mode of pathogenicity: None; Publications: 16570191, 15024724; Phenotypes: Ceroid lipofuscinosis, neuronal, 8, MIM# 600143, Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.116 PSTPIP1 Zornitza Stark Phenotypes for gene: PSTPIP1 were changed from Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416 to Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979; Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416
BabyScreen+ newborn screening v1.115 PSTPIP1 Zornitza Stark edited their review of gene: PSTPIP1: Changed phenotypes: Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416, Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979
BabyScreen+ newborn screening v1.115 THAP11 Zornitza Stark Phenotypes for gene: THAP11 were changed from Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related to Methylmalonic aciduria, cblC type-like, MIM# 620940; Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related
BabyScreen+ newborn screening v1.114 THAP11 Zornitza Stark reviewed gene: THAP11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Methylmalonic aciduria, cblC type-like, MIM# 620940, Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.114 AHCY Carolyn Bursle reviewed gene: AHCY: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
BabyScreen+ newborn screening v1.114 GCH1 Lilian Downie Mode of inheritance for gene: GCH1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.113 GCH1 Lilian Downie reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301681; Phenotypes: Dystonia, DOPA-responsive MIM#128230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.113 LIG4 Zornitza Stark Publications for gene: LIG4 were set to 16088910; 9823897; 10911993; 15333585; 9809069, 12023982; 11040211; 15175260; 19451691; 17554302; 11779494
BabyScreen+ newborn screening v1.112 LIG4 Zornitza Stark Publications for gene: LIG4 were set to
BabyScreen+ newborn screening v1.111 LIG4 Santosh Varughese reviewed gene: LIG4: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, 15175260, 19451691, 17554302, 11779494; Phenotypes: LIG4 SYNDROME, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.111 ELANE Zornitza Stark Mode of pathogenicity for gene: ELANE was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
BabyScreen+ newborn screening v1.110 ELANE Zornitza Stark commented on gene: ELANE: ClinGen: there is little evidence for haploinsufficiency. gnomAD pLI score is zero and there are NMD predicted variants in the population.

Entire gene deletion is not described in the context of neutropenia, including deletion of 19p terminal (encompassing ELANE) (PMID: 33968054).

Maturation arrest, the failure of the marrow myeloid progenitors to form mature neutrophils, is a consistent feature of ELANE associated congenital neutropenia. Knock-out of the mutant allele in hematopoietic stem cells derived from SCN patients restores neutrophils maturation (PMID: 3124897).
BabyScreen+ newborn screening v1.110 ELANE Zornitza Stark edited their review of gene: ELANE: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
BabyScreen+ newborn screening v1.110 TSHR Zornitza Stark Phenotypes for gene: TSHR were changed from Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200; HYPERTHYROIDISM, FAMILIAL GESTATIONAL HYPERTHYROIDISM to Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200
BabyScreen+ newborn screening v1.109 TSHR Zornitza Stark Mode of inheritance for gene: TSHR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.108 TSHR Zornitza Stark edited their review of gene: TSHR: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.108 CBS Zornitza Stark Classified gene: CBS as Green List (high evidence)
BabyScreen+ newborn screening v1.108 CBS Zornitza Stark Gene: cbs has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.107 CBS Zornitza Stark edited their review of gene: CBS: Added comment: Upgraded to Green following reassessment of mapping issues on WGS vs ES.; Changed rating: GREEN
BabyScreen+ newborn screening v1.107 WNK1 Zornitza Stark Marked gene: WNK1 as ready
BabyScreen+ newborn screening v1.107 WNK1 Zornitza Stark Gene: wnk1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.107 WNK1 Zornitza Stark Phenotypes for gene: WNK1 were changed from Neuropathy, hereditary sensory and autonomic, type I to Pseudohypoaldosteronism 2C (PHA2C), MIM#614492
BabyScreen+ newborn screening v1.106 WNK1 Zornitza Stark Mode of inheritance for gene: WNK1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.105 WNK1 Zornitza Stark Classified gene: WNK1 as Green List (high evidence)
BabyScreen+ newborn screening v1.105 WNK1 Zornitza Stark Gene: wnk1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.104 WNK1 Zornitza Stark Tag treatable tag was added to gene: WNK1.
Tag endocrine tag was added to gene: WNK1.
BabyScreen+ newborn screening v1.104 WNK1 Zornitza Stark reviewed gene: WNK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudohypoaldosteronism 2C (PHA2C), MIM#614492; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.104 TRIM28 Zornitza Stark Marked gene: TRIM28 as ready
BabyScreen+ newborn screening v1.104 TRIM28 Zornitza Stark Gene: trim28 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.104 TRIM28 Zornitza Stark Classified gene: TRIM28 as Green List (high evidence)
BabyScreen+ newborn screening v1.104 TRIM28 Zornitza Stark Gene: trim28 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.103 TRIM28 Zornitza Stark Tag cancer tag was added to gene: TRIM28.
Tag treatable tag was added to gene: TRIM28.
BabyScreen+ newborn screening v1.103 TRIM28 Zornitza Stark gene: TRIM28 was added
gene: TRIM28 was added to BabyScreen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TRIM28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM28 were set to 30694527
Phenotypes for gene: TRIM28 were set to Wilms tumour, MONDO:0006058, TRIM28-related
Review for gene: TRIM28 was set to GREEN
Added comment: Established gene-disease association, more than 10 individuals reported.

Onset in childhood.

Included for completeness as managed similarly to WT1.
Sources: Expert list
BabyScreen+ newborn screening v1.102 TRHR Zornitza Stark Marked gene: TRHR as ready
BabyScreen+ newborn screening v1.102 TRHR Zornitza Stark Gene: trhr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.102 TRHR Zornitza Stark Phenotypes for gene: TRHR were changed from Thyrotropin-releasing hormone resistance, generalized to Hypothyroidism, congenital, nongoitrous, 7, MIM# 618573
BabyScreen+ newborn screening v1.101 TRHR Zornitza Stark Publications for gene: TRHR were set to
BabyScreen+ newborn screening v1.100 TRHR Zornitza Stark Classified gene: TRHR as Green List (high evidence)
BabyScreen+ newborn screening v1.100 TRHR Zornitza Stark Gene: trhr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.99 TRHR Zornitza Stark Tag treatable tag was added to gene: TRHR.
Tag endocrine tag was added to gene: TRHR.
BabyScreen+ newborn screening v1.99 TRHR Zornitza Stark reviewed gene: TRHR: Rating: GREEN; Mode of pathogenicity: None; Publications: 9141550, 19213692, 26735259, 28419241, 32319661; Phenotypes: Hypothyroidism, congenital, nongoitrous, 7, MIM# 618573; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.99 SGPL1 Zornitza Stark Classified gene: SGPL1 as Green List (high evidence)
BabyScreen+ newborn screening v1.99 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.98 SGPL1 Zornitza Stark Tag renal was removed from gene: SGPL1.
Tag treatable tag was added to gene: SGPL1.
Tag endocrine tag was added to gene: SGPL1.
BabyScreen+ newborn screening v1.98 SGPL1 Zornitza Stark reviewed gene: SGPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephrotic syndrome, type 14 MIM#617575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.98 SCNN1G Zornitza Stark Marked gene: SCNN1G as ready
BabyScreen+ newborn screening v1.98 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.98 SCNN1G Zornitza Stark Phenotypes for gene: SCNN1G were changed from Pseudohypoaldosteronism, type I, MIM# 264350; Pseudohypoaldosteronism to Pseudohypoaldosteronism, type I, MIM# 264350
BabyScreen+ newborn screening v1.97 SCNN1G Zornitza Stark Classified gene: SCNN1G as Green List (high evidence)
BabyScreen+ newborn screening v1.97 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.96 SCNN1G Zornitza Stark Tag treatable tag was added to gene: SCNN1G.
Tag endocrine tag was added to gene: SCNN1G.
BabyScreen+ newborn screening v1.96 SCNN1G Zornitza Stark reviewed gene: SCNN1G: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudohypoaldosteronism, type I, MIM# 264350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.96 RPS7 Zornitza Stark Marked gene: RPS7 as ready
BabyScreen+ newborn screening v1.96 RPS7 Zornitza Stark Gene: rps7 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.96 RPS7 Zornitza Stark Phenotypes for gene: RPS7 were changed from Diamond-Blackfan anaemia 8, MIM# 612563; Diamond-Blackfan anemia to Diamond-Blackfan anaemia 8, MIM# 612563
BabyScreen+ newborn screening v1.95 RPS7 Zornitza Stark Publications for gene: RPS7 were set to
BabyScreen+ newborn screening v1.94 RPS7 Zornitza Stark Classified gene: RPS7 as Green List (high evidence)
BabyScreen+ newborn screening v1.94 RPS7 Zornitza Stark Gene: rps7 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.93 RPS7 Zornitza Stark Tag treatable tag was added to gene: RPS7.
Tag haematological tag was added to gene: RPS7.
BabyScreen+ newborn screening v1.93 RPS7 Zornitza Stark reviewed gene: RPS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 19061985, 23718193, 27882484, 32772263; Phenotypes: Diamond-Blackfan anemia 8, MIM# 612563; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.93 RPL35A Zornitza Stark Marked gene: RPL35A as ready
BabyScreen+ newborn screening v1.93 RPL35A Zornitza Stark Gene: rpl35a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.93 RPL35A Zornitza Stark Phenotypes for gene: RPL35A were changed from Diamond-Blackfan anaemia 5, MIM# 612528; Diamond-Blackfan anemia to Diamond-Blackfan anaemia 5, MIM# 612528
BabyScreen+ newborn screening v1.92 RPL35A Zornitza Stark Publications for gene: RPL35A were set to
BabyScreen+ newborn screening v1.91 RPL35A Zornitza Stark Classified gene: RPL35A as Green List (high evidence)
BabyScreen+ newborn screening v1.91 RPL35A Zornitza Stark Gene: rpl35a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.90 RPL35A Zornitza Stark Tag treatable tag was added to gene: RPL35A.
Tag haematological tag was added to gene: RPL35A.
BabyScreen+ newborn screening v1.90 RPL35A Zornitza Stark reviewed gene: RPL35A: Rating: GREEN; Mode of pathogenicity: None; Publications: 18535205, 32241839; Phenotypes: Diamond-Blackfan anemia 5, MIM# 612528; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.90 REST Zornitza Stark Marked gene: REST as ready
BabyScreen+ newborn screening v1.90 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.90 REST Zornitza Stark Classified gene: REST as Green List (high evidence)
BabyScreen+ newborn screening v1.90 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.89 REST Zornitza Stark gene: REST was added
gene: REST was added to BabyScreen+ newborn screening. Sources: Expert list
cancer, treatable tags were added to gene: REST.
Mode of inheritance for gene: REST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REST were set to 26551668; 34308104
Phenotypes for gene: REST were set to {Wilms tumor 6, susceptibility to}, MIM# 616806
Review for gene: REST was set to GREEN
Added comment: Established association, more than 10 families reported.

Childhood onset.

Included for completeness as managed similarly to WT1.
Sources: Expert list
BabyScreen+ newborn screening v1.88 PSTPIP1 Zornitza Stark Marked gene: PSTPIP1 as ready
BabyScreen+ newborn screening v1.88 PSTPIP1 Zornitza Stark Gene: pstpip1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.88 PSTPIP1 Zornitza Stark Classified gene: PSTPIP1 as Green List (high evidence)
BabyScreen+ newborn screening v1.88 PSTPIP1 Zornitza Stark Gene: pstpip1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.87 PSTPIP1 Zornitza Stark gene: PSTPIP1 was added
gene: PSTPIP1 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: PSTPIP1.
Mode of inheritance for gene: PSTPIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PSTPIP1 were set to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416
Review for gene: PSTPIP1 was set to GREEN
Added comment: Established gene-disease association.

Onset in childhood.

Treatment: adalimumab and tacrolimus, NSAIDs, corticosteroids, BMT

non-genetic confirmatory testing: no
Sources: Expert list
BabyScreen+ newborn screening v1.86 PPOX Zornitza Stark Marked gene: PPOX as ready
BabyScreen+ newborn screening v1.86 PPOX Zornitza Stark Gene: ppox has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.86 PPOX Zornitza Stark Phenotypes for gene: PPOX were changed from Porphyria variegata to Variegate porphyria, childhood-onset, MIM# 620483
BabyScreen+ newborn screening v1.85 PPOX Zornitza Stark Tag treatable tag was added to gene: PPOX.
Tag haematological tag was added to gene: PPOX.
BabyScreen+ newborn screening v1.85 PPOX Zornitza Stark Mode of inheritance for gene: PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.84 PPOX Zornitza Stark Classified gene: PPOX as Green List (high evidence)
BabyScreen+ newborn screening v1.84 PPOX Zornitza Stark Gene: ppox has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.83 PPOX Zornitza Stark reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Variegate porphyria, childhood-onset, MIM# 620483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.83 POMC Zornitza Stark Marked gene: POMC as ready
BabyScreen+ newborn screening v1.83 POMC Zornitza Stark Gene: pomc has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.83 POMC Zornitza Stark Phenotypes for gene: POMC were changed from Proopiomelanocortin deficiency to Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734
BabyScreen+ newborn screening v1.82 POMC Zornitza Stark Classified gene: POMC as Green List (high evidence)
BabyScreen+ newborn screening v1.82 POMC Zornitza Stark Gene: pomc has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.81 POMC Zornitza Stark reviewed gene: POMC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.81 POLE Zornitza Stark Marked gene: POLE as ready
BabyScreen+ newborn screening v1.81 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.81 POLE Zornitza Stark Classified gene: POLE as Green List (high evidence)
BabyScreen+ newborn screening v1.81 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.80 POLE Zornitza Stark gene: POLE was added
gene: POLE was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: POLE.
Mode of inheritance for gene: POLE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLE were set to IMAGE-I syndrome, MIM# 618336
Review for gene: POLE was set to GREEN
Added comment: Established gene-disease association.

Multi-system disorder comprising GH and adrenal hypoplasia.

Treatment: hydrocortisone

non-genetic confirmatory testing: hormone levels
Sources: Expert list
BabyScreen+ newborn screening v1.79 NCF4 Zornitza Stark Marked gene: NCF4 as ready
BabyScreen+ newborn screening v1.79 NCF4 Zornitza Stark Gene: ncf4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.79 NCF4 Zornitza Stark Phenotypes for gene: NCF4 were changed from Chronic granulomatous disease 3, autosomal recessive, MIM# 613960; Chronic granulomatous disease to Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960
BabyScreen+ newborn screening v1.78 NCF4 Zornitza Stark Classified gene: NCF4 as Green List (high evidence)
BabyScreen+ newborn screening v1.78 NCF4 Zornitza Stark Gene: ncf4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.77 NCF4 Zornitza Stark Tag treatable tag was added to gene: NCF4.
Tag immunological tag was added to gene: NCF4.
BabyScreen+ newborn screening v1.77 NCF4 Zornitza Stark reviewed gene: NCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.77 LPL Zornitza Stark Marked gene: LPL as ready
BabyScreen+ newborn screening v1.77 LPL Zornitza Stark Gene: lpl has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.77 LPL Zornitza Stark Classified gene: LPL as Green List (high evidence)
BabyScreen+ newborn screening v1.77 LPL Zornitza Stark Gene: lpl has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.76 LPL Zornitza Stark gene: LPL was added
gene: LPL was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: LPL.
Mode of inheritance for gene: LPL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LPL were set to Lipoprotein lipase deficiency, MIM# 238600
Review for gene: LPL was set to GREEN
Added comment: Established gene-disease association.

Bi-allelic disease is severe and presents in infancy.

Treatment: volanesorsen, dietary fat restriction, lomitapide

Non-genetic confirmatory testing: LPL activity
Sources: Expert list
BabyScreen+ newborn screening v1.75 LAT Zornitza Stark Marked gene: LAT as ready
BabyScreen+ newborn screening v1.75 LAT Zornitza Stark Gene: lat has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.75 LAT Zornitza Stark Classified gene: LAT as Green List (high evidence)
BabyScreen+ newborn screening v1.75 LAT Zornitza Stark Gene: lat has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.74 LAT Zornitza Stark gene: LAT was added
gene: LAT was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: LAT.
Mode of inheritance for gene: LAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LAT were set to Immunodeficiency 52, MIM# 617514
Review for gene: LAT was set to GREEN
Added comment: Established gene-disease association.

SCID-like presentation.

Treatment: BMT

Non-genetic confirmatory testing: yes
Sources: Expert list
BabyScreen+ newborn screening v1.73 KLHL3 Zornitza Stark Marked gene: KLHL3 as ready
BabyScreen+ newborn screening v1.73 KLHL3 Zornitza Stark Gene: klhl3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.73 KLHL3 Zornitza Stark Classified gene: KLHL3 as Green List (high evidence)
BabyScreen+ newborn screening v1.73 KLHL3 Zornitza Stark Gene: klhl3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.72 KLHL3 Zornitza Stark gene: KLHL3 was added
gene: KLHL3 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: KLHL3.
Mode of inheritance for gene: KLHL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: KLHL3 were set to Pseudohypoaldosteronism, type IID, MIM# 614495
Review for gene: KLHL3 was set to GREEN
Added comment: Established gene disease association.

Results in hyperkalaemia and later, the development of hypertension.

Treatment: thiazide diuretics normalise electrolytes

Non-genetic confirmatory testing: electrolytes
Sources: Expert list
BabyScreen+ newborn screening v1.71 IRF8 Zornitza Stark Marked gene: IRF8 as ready
BabyScreen+ newborn screening v1.71 IRF8 Zornitza Stark Gene: irf8 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.71 IRF8 Zornitza Stark Classified gene: IRF8 as Green List (high evidence)
BabyScreen+ newborn screening v1.71 IRF8 Zornitza Stark Gene: irf8 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.70 IRF8 Zornitza Stark gene: IRF8 was added
gene: IRF8 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IRF8.
Mode of inheritance for gene: IRF8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRF8 were set to Immunodeficiency 32B, monocyte and dendritic cell deficiency, autosomal recessive, MIM# 226990
Review for gene: IRF8 was set to GREEN
Added comment: At least 4 families reported with bi-allelic variants. Gene-disease association also proposed for mono-allelic variants but only two individuals reported.

Recurrent infections presenting in infancy.

Treatment: BMT

Non-genetic confirmatory testing available
Sources: Expert list
BabyScreen+ newborn screening v1.69 IL10RB Zornitza Stark Marked gene: IL10RB as ready
BabyScreen+ newborn screening v1.69 IL10RB Zornitza Stark Gene: il10rb has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.69 IL10RB Zornitza Stark Phenotypes for gene: IL10RB were changed from Inflammatory bowel disease; Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567 to Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567
BabyScreen+ newborn screening v1.68 IL10RB Zornitza Stark Classified gene: IL10RB as Green List (high evidence)
BabyScreen+ newborn screening v1.68 IL10RB Zornitza Stark Gene: il10rb has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.67 IL10RB Zornitza Stark Tag treatable tag was added to gene: IL10RB.
Tag immunological tag was added to gene: IL10RB.
BabyScreen+ newborn screening v1.67 IL10RB Zornitza Stark reviewed gene: IL10RB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.67 IL10 Zornitza Stark Marked gene: IL10 as ready
BabyScreen+ newborn screening v1.67 IL10 Zornitza Stark Gene: il10 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.67 IL10 Zornitza Stark Classified gene: IL10 as Green List (high evidence)
BabyScreen+ newborn screening v1.67 IL10 Zornitza Stark Gene: il10 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.66 IL10 Zornitza Stark Tag treatable tag was added to gene: IL10.
Tag immunological tag was added to gene: IL10.
BabyScreen+ newborn screening v1.66 IL10 Zornitza Stark gene: IL10 was added
gene: IL10 was added to BabyScreen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: IL10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL10 were set to 22236434; 20951137; 19890111
Phenotypes for gene: IL10 were set to Autoinflammatory syndrome, MONDO:0019751, IL10-related
Review for gene: IL10 was set to GREEN
Added comment: Established gene-disease association.

Onset in infancy and childhood.

Treatment: BMT

Non-genetic confirmatory testing: flow cytometry
Sources: Expert list
BabyScreen+ newborn screening v1.65 IGF1 Zornitza Stark Marked gene: IGF1 as ready
BabyScreen+ newborn screening v1.65 IGF1 Zornitza Stark Gene: igf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.65 IGF1 Zornitza Stark Phenotypes for gene: IGF1 were changed from Insulin-like growth factor deficiency to Insulin-like growth factor I deficiency, MIM# 608747
BabyScreen+ newborn screening v1.64 IGF1 Zornitza Stark Classified gene: IGF1 as Green List (high evidence)
BabyScreen+ newborn screening v1.64 IGF1 Zornitza Stark Gene: igf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.63 IGF1 Zornitza Stark Tag treatable tag was added to gene: IGF1.
Tag endocrine tag was added to gene: IGF1.
BabyScreen+ newborn screening v1.63 IGF1 Zornitza Stark reviewed gene: IGF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Insulin-like growth factor I deficiency, MIM# 608747; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.63 GALNT3 Zornitza Stark Marked gene: GALNT3 as ready
BabyScreen+ newborn screening v1.63 GALNT3 Zornitza Stark Gene: galnt3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.63 GALNT3 Zornitza Stark Classified gene: GALNT3 as Green List (high evidence)
BabyScreen+ newborn screening v1.63 GALNT3 Zornitza Stark Gene: galnt3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.62 GALNT3 Zornitza Stark gene: GALNT3 was added
gene: GALNT3 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: GALNT3.
Mode of inheritance for gene: GALNT3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALNT3 were set to Tumoral calcinosis, hyperphosphatemic, familial, 1, MIM# 211900
Review for gene: GALNT3 was set to GREEN
Added comment: Established gene-disease association.

Onset in infancy/childhood.

Treatment: dietary restriction, phosphate binders, acetazolamide

Non-genetic confirmatory testing: serum phosphate, calcium, PTH, alkaline phosphatase, vitamin D serum levels, urine calcium, phosphate levels, plasma levels of the C-terminal portion of the phosphate-regulating hormone, fibroblast growth factor 23
Sources: Expert list
BabyScreen+ newborn screening v1.61 FECH Zornitza Stark Marked gene: FECH as ready
BabyScreen+ newborn screening v1.61 FECH Zornitza Stark Gene: fech has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.61 FECH Zornitza Stark Classified gene: FECH as Green List (high evidence)
BabyScreen+ newborn screening v1.61 FECH Zornitza Stark Gene: fech has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.60 FECH Zornitza Stark gene: FECH was added
gene: FECH was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, haematological tags were added to gene: FECH.
Mode of inheritance for gene: FECH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FECH were set to Protoporphyria, erythropoietic, 1, MIM# 177000
Review for gene: FECH was set to GREEN
Added comment: Established gene-disease association.

Onset of photosensitivity is in infancy/childhood.

Treatment: Afamelanotide

Non-genetic confirmatory testing: free protoporphyrin
Sources: Expert list
BabyScreen+ newborn screening v1.59 F13B Zornitza Stark Marked gene: F13B as ready
BabyScreen+ newborn screening v1.59 F13B Zornitza Stark Gene: f13b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.59 F13B Zornitza Stark Phenotypes for gene: F13B were changed from Factor XIIIB deficiency MIM# 613235; Factor XIIIB deficiency, MIM# 613235 to Factor XIIIB deficiency, MIM#613235
BabyScreen+ newborn screening v1.58 F13B Zornitza Stark Classified gene: F13B as Green List (high evidence)
BabyScreen+ newborn screening v1.58 F13B Zornitza Stark Gene: f13b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.57 F13B Zornitza Stark Tag treatable tag was added to gene: F13B.
Tag haematological tag was added to gene: F13B.
BabyScreen+ newborn screening v1.57 F13B Zornitza Stark reviewed gene: F13B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor XIIIB deficiency, MIM#613235; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.57 F10 Zornitza Stark Classified gene: F10 as Green List (high evidence)
BabyScreen+ newborn screening v1.57 F10 Zornitza Stark Gene: f10 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.56 F10 Zornitza Stark Tag for review was removed from gene: F10.
Tag treatable tag was added to gene: F10.
Tag haematological tag was added to gene: F10.
BabyScreen+ newborn screening v1.56 F10 Zornitza Stark changed review comment from: Well established gene-disease association.

Variable severity: for review. Affected individuals can manifest prolonged nasal and mucosal haemorrhage, menorrhagia, haematuria, and occasionally hemarthrosis.

Treatment: plasma-derived factor 10 concentrate (Coagadex); to: Well established gene-disease association.

Affected individuals can manifest prolonged nasal and mucosal haemorrhage, menorrhagia, haematuria, and occasionally hemarthrosis.

Treatment: plasma-derived factor 10 concentrate (Coagadex)
BabyScreen+ newborn screening v1.56 F10 Zornitza Stark edited their review of gene: F10: Changed rating: GREEN
BabyScreen+ newborn screening v1.56 ERCC4 Zornitza Stark Marked gene: ERCC4 as ready
BabyScreen+ newborn screening v1.56 ERCC4 Zornitza Stark Gene: ercc4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.56 ERCC4 Zornitza Stark Phenotypes for gene: ERCC4 were changed from Xeroderma pigmentosum, group F, MIM# 278760; Xeroderma pigmentosum; Fanconi anaemia, complementation group Q, MIM# 615272 to Fanconi anemia, complementation group Q, MIM# 615272
BabyScreen+ newborn screening v1.55 ERCC4 Zornitza Stark Classified gene: ERCC4 as Green List (high evidence)
BabyScreen+ newborn screening v1.55 ERCC4 Zornitza Stark Gene: ercc4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.54 ERCC4 Zornitza Stark Tag treatable tag was added to gene: ERCC4.
Tag haematological tag was added to gene: ERCC4.
BabyScreen+ newborn screening v1.54 ERCC4 Zornitza Stark reviewed gene: ERCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group Q, MIM# 615272; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.54 CYP7B1 Zornitza Stark Marked gene: CYP7B1 as ready
BabyScreen+ newborn screening v1.54 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.54 CYP7B1 Zornitza Stark Phenotypes for gene: CYP7B1 were changed from Cholestasis, severe to Bile acid synthesis defect, congenital, 3, MIM# 613812
BabyScreen+ newborn screening v1.53 CYP7B1 Zornitza Stark Publications for gene: CYP7B1 were set to
BabyScreen+ newborn screening v1.52 CYP7B1 Zornitza Stark Classified gene: CYP7B1 as Green List (high evidence)
BabyScreen+ newborn screening v1.52 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.51 CYP7B1 Zornitza Stark Tag treatable tag was added to gene: CYP7B1.
Tag liver tag was added to gene: CYP7B1.
BabyScreen+ newborn screening v1.51 CYP7B1 Zornitza Stark reviewed gene: CYP7B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24658845, 31337596, 30366773, 9802883; Phenotypes: Bile acid synthesis defect, congenital, 3, MIM# 613812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.51 CUL3 Zornitza Stark Marked gene: CUL3 as ready
BabyScreen+ newborn screening v1.51 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.51 CUL3 Zornitza Stark Classified gene: CUL3 as Green List (high evidence)
BabyScreen+ newborn screening v1.51 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.50 CUL3 Zornitza Stark gene: CUL3 was added
gene: CUL3 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: CUL3.
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CUL3 were set to Pseudohypoaldosteronism, type IIE 614496
Review for gene: CUL3 was set to GREEN
Added comment: Established gene-disease association.

Variants in this gene also cause a neurodevelopmental disorder; however, there is some genotype-phenotype correlation literature to help distinguish the two.

Results in hyperkalaemia and development of hypertension. However, the onset of hypertension is generally later in life.

Treatment: thiazide diuretics normalise biochemical abnormalities
Sources: Expert list
BabyScreen+ newborn screening v1.48 COQ6 Zornitza Stark Marked gene: COQ6 as ready
BabyScreen+ newborn screening v1.48 COQ6 Zornitza Stark Gene: coq6 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.48 COQ6 Zornitza Stark Phenotypes for gene: COQ6 were changed from Nephrotic syndrome with sensorineural deafness; Coenzyme Q10 deficiency, primary, 6, MIM# 614650 to Coenzyme Q10 deficiency, primary, 6, MIM# 614650
BabyScreen+ newborn screening v1.47 COQ6 Zornitza Stark Classified gene: COQ6 as Green List (high evidence)
BabyScreen+ newborn screening v1.47 COQ6 Zornitza Stark Gene: coq6 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.46 COQ6 Zornitza Stark Tag treatable tag was added to gene: COQ6.
Tag metabolic tag was added to gene: COQ6.
BabyScreen+ newborn screening v1.46 COQ6 Zornitza Stark reviewed gene: COQ6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 6 MIM#614650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.46 COQ2 Zornitza Stark Marked gene: COQ2 as ready
BabyScreen+ newborn screening v1.46 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.46 COQ2 Zornitza Stark Phenotypes for gene: COQ2 were changed from Coenzyme Q10 deficiency, primary, 1, MIM# 607426; Coenzyme Q10 deficiency, primary, 1 to Coenzyme Q10 deficiency, primary, 1, MIM# 607426
BabyScreen+ newborn screening v1.45 COQ2 Zornitza Stark Classified gene: COQ2 as Green List (high evidence)
BabyScreen+ newborn screening v1.45 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.44 COQ2 Zornitza Stark Tag treatable tag was added to gene: COQ2.
Tag metabolic tag was added to gene: COQ2.
BabyScreen+ newborn screening v1.44 COQ2 Zornitza Stark reviewed gene: COQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 1, MIM# 607426; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.44 CHRNB1 Zornitza Stark Marked gene: CHRNB1 as ready
BabyScreen+ newborn screening v1.44 CHRNB1 Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.44 CHRNB1 Zornitza Stark Classified gene: CHRNB1 as Green List (high evidence)
BabyScreen+ newborn screening v1.44 CHRNB1 Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.43 CHRNB1 Zornitza Stark Tag treatable tag was added to gene: CHRNB1.
Tag neurological tag was added to gene: CHRNB1.
BabyScreen+ newborn screening v1.43 CHRNB1 Zornitza Stark reviewed gene: CHRNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32895905; Phenotypes: Myasthenic syndrome, slow-channel congenital, 601462 Myasthenic syndrome, congenital, 2A, slow-channel, 616313, Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.43 CFI Zornitza Stark Marked gene: CFI as ready
BabyScreen+ newborn screening v1.43 CFI Zornitza Stark Gene: cfi has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.43 CFI Zornitza Stark Phenotypes for gene: CFI were changed from Haemolytic uraemic syndrome to Complement factor I deficiency MIM#610984
BabyScreen+ newborn screening v1.42 CFI Zornitza Stark Classified gene: CFI as Green List (high evidence)
BabyScreen+ newborn screening v1.42 CFI Zornitza Stark Gene: cfi has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.41 CFI Zornitza Stark reviewed gene: CFI: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Complement factor I deficiency MIM#610984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.41 CFH Zornitza Stark Marked gene: CFH as ready
BabyScreen+ newborn screening v1.41 CFH Zornitza Stark Gene: cfh has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.41 CFH Zornitza Stark Phenotypes for gene: CFH were changed from Haemolytic uraemic syndrome to Complement factor H deficiency, MIM# 609814
BabyScreen+ newborn screening v1.40 CFH Zornitza Stark Classified gene: CFH as Green List (high evidence)
BabyScreen+ newborn screening v1.40 CFH Zornitza Stark Gene: cfh has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.39 CFH Zornitza Stark Tag treatable tag was added to gene: CFH.
Tag immunological tag was added to gene: CFH.
BabyScreen+ newborn screening v1.39 CFH Zornitza Stark reviewed gene: CFH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Complement factor H deficiency, MIM# 609814; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.39 CFD Zornitza Stark Marked gene: CFD as ready
BabyScreen+ newborn screening v1.39 CFD Zornitza Stark Gene: cfd has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.39 CFD Zornitza Stark Phenotypes for gene: CFD were changed from Complement factor D deficiency, MIM# 613912; Complement factor D deficiency to Complement factor D deficiency, MIM# 613912
BabyScreen+ newborn screening v1.38 CFD Zornitza Stark Publications for gene: CFD were set to
BabyScreen+ newborn screening v1.37 CFD Zornitza Stark Classified gene: CFD as Green List (high evidence)
BabyScreen+ newborn screening v1.37 CFD Zornitza Stark Gene: cfd has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.36 CFD Zornitza Stark Tag treatable tag was added to gene: CFD.
Tag immunological tag was added to gene: CFD.
BabyScreen+ newborn screening v1.36 CFD Zornitza Stark reviewed gene: CFD: Rating: GREEN; Mode of pathogenicity: None; Publications: 11457876, 16527897, 31440263; Phenotypes: Complement factor D deficiency, MIM# 613912; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.36 CEBPE Zornitza Stark Marked gene: CEBPE as ready
BabyScreen+ newborn screening v1.36 CEBPE Zornitza Stark Gene: cebpe has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.36 CEBPE Zornitza Stark Classified gene: CEBPE as Green List (high evidence)
BabyScreen+ newborn screening v1.36 CEBPE Zornitza Stark Gene: cebpe has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.35 CEBPE Zornitza Stark Tag treatable tag was added to gene: CEBPE.
Tag immunological tag was added to gene: CEBPE.
BabyScreen+ newborn screening v1.35 CEBPE Zornitza Stark gene: CEBPE was added
gene: CEBPE was added to BabyScreen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: CEBPE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEBPE were set to Specific granule deficiency, MIM# 245480
Review for gene: CEBPE was set to GREEN
Added comment: Established gene-disease association.

Recurrent infections in infancy and childhood.

Treatment: long term antimicrobial prophalaxis

Non-genetic confirmatory testing available
Sources: Expert Review
BabyScreen+ newborn screening v1.34 C3 Zornitza Stark Marked gene: C3 as ready
BabyScreen+ newborn screening v1.34 C3 Zornitza Stark Gene: c3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.34 C3 Zornitza Stark Phenotypes for gene: C3 were changed from Haemolytic uraemic syndrome; C3 deficiency, MIM# 613779 to C3 deficiency, MIM# 613779
BabyScreen+ newborn screening v1.33 C3 Zornitza Stark Classified gene: C3 as Green List (high evidence)
BabyScreen+ newborn screening v1.33 C3 Zornitza Stark Gene: c3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.32 C3 Zornitza Stark Tag treatable tag was added to gene: C3.
Tag immunological tag was added to gene: C3.
BabyScreen+ newborn screening v1.32 C3 Zornitza Stark reviewed gene: C3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: C3 deficiency, MIM# 613779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.32 C2 Zornitza Stark Marked gene: C2 as ready
BabyScreen+ newborn screening v1.32 C2 Zornitza Stark Gene: c2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.32 C2 Zornitza Stark Classified gene: C2 as Green List (high evidence)
BabyScreen+ newborn screening v1.32 C2 Zornitza Stark Gene: c2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.31 C2 Zornitza Stark Tag treatable tag was added to gene: C2.
Tag immunological tag was added to gene: C2.
BabyScreen+ newborn screening v1.31 C2 Zornitza Stark gene: C2 was added
gene: C2 was added to BabyScreen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: C2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2 were set to 31421540
Phenotypes for gene: C2 were set to C2 deficiency, MIM# 217000
Review for gene: C2 was set to GREEN
Added comment: Established gene-disease association.

Can present with severe early infections in infancy/childhood.

Later manifestations include autoimmune phenomena.

Treatment: pneumococcal, meningococcal, haemophilus influenzae vaccines

Non-genetic confirmatory tests: complement levels
Sources: Expert list
BabyScreen+ newborn screening v1.30 APOA5 Zornitza Stark Marked gene: APOA5 as ready
BabyScreen+ newborn screening v1.30 APOA5 Zornitza Stark Gene: apoa5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.30 APOA5 Zornitza Stark gene: APOA5 was added
gene: APOA5 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable tags were added to gene: APOA5.
Mode of inheritance for gene: APOA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOA5 were set to 23307945; 31390500
Phenotypes for gene: APOA5 were set to Hyperchylomicronaemia, late-onset, MIM# 144650
Review for gene: APOA5 was set to RED
Added comment: Established gene-disease association.

Variable age of onset, many of the reported individuals are adults.

Treatment: Volanesorsen
Sources: Expert list
BabyScreen+ newborn screening v1.29 AP3D1 Zornitza Stark Marked gene: AP3D1 as ready
BabyScreen+ newborn screening v1.29 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.29 AP3D1 Zornitza Stark Classified gene: AP3D1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v1.29 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.28 AP3D1 Zornitza Stark gene: AP3D1 was added
gene: AP3D1 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, haematological tags were added to gene: AP3D1.
Mode of inheritance for gene: AP3D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP3D1 were set to 26744459; 9697856; 30472485; 36445457
Phenotypes for gene: AP3D1 were set to Hermansky-Pudlak syndrome 10, MIM# 617050
Review for gene: AP3D1 was set to AMBER
Added comment: Four individuals from two unrelated families and a mouse model. Borderline gene-disease association.

New case report 36445457, proband presenting with SNHL and questionable other subtle features of HPS, homozygous missense variant (VOUS).

Onset in infancy.

Treatable: BMT for immunodeficiency.
Sources: Expert list
BabyScreen+ newborn screening v1.27 AMACR Zornitza Stark Marked gene: AMACR as ready
BabyScreen+ newborn screening v1.27 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.27 AMACR Zornitza Stark Phenotypes for gene: AMACR were changed from Alpha-methylacyl-CoA racemase deficiency; Bile acid synthesis defect, congenital, 4 to Bile acid synthesis defect, congenital, 4, MIM# 214950
BabyScreen+ newborn screening v1.26 AMACR Zornitza Stark Publications for gene: AMACR were set to
BabyScreen+ newborn screening v1.25 AMACR Zornitza Stark Classified gene: AMACR as Green List (high evidence)
BabyScreen+ newborn screening v1.25 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.24 AMACR Zornitza Stark Tag treatable tag was added to gene: AMACR.
Tag liver tag was added to gene: AMACR.
BabyScreen+ newborn screening v1.24 AMACR Zornitza Stark reviewed gene: AMACR: Rating: GREEN; Mode of pathogenicity: None; Publications: 12512044; Phenotypes: Bile acid synthesis defect, congenital, 4, MIM# 214950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v1.24 ABCD4 Zornitza Stark Tag treatable tag was added to gene: ABCD4.
BabyScreen+ newborn screening v1.24 SLC9A3 Zornitza Stark edited their review of gene: SLC9A3: Changed rating: AMBER
BabyScreen+ newborn screening v1.24 SLC9A3 Zornitza Stark commented on gene: SLC9A3
BabyScreen+ newborn screening v1.24 ATRX Zornitza Stark edited their review of gene: ATRX: Changed phenotypes: ATR-X-related syndrome MONDO:0016980
BabyScreen+ newborn screening v1.24 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580 to ATR-X-related syndrome MONDO:0016980
BabyScreen+ newborn screening v1.23 TRAC Zornitza Stark Marked gene: TRAC as ready
BabyScreen+ newborn screening v1.23 TRAC Zornitza Stark Gene: trac has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.23 TRAC Zornitza Stark gene: TRAC was added
gene: TRAC was added to BabyScreen+ newborn screening. Sources: Expert Review
founder, technically challenging tags were added to gene: TRAC.
Mode of inheritance for gene: TRAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAC were set to 21206088
Phenotypes for gene: TRAC were set to Immunodeficiency 7, TCR-alpha/beta deficient, MIM#615387
Review for gene: TRAC was set to RED
Added comment: Single variant reported to date in 6 patients; 2 unrelated children from consanguineous families of Pakistani descent (PMID: 21206088); 1 non-consanguineous family from North-west India (PMID: 33909184) and 1 consanguineous parents of East Indian (https://lymphosign.com/doi/10.14785/lymphosign-2022-0001)

Also note annotation issues in certain variant curation and annotation tools.
Sources: Expert Review
BabyScreen+ newborn screening v1.22 NCF1 Zornitza Stark Classified gene: NCF1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v1.22 NCF1 Zornitza Stark Gene: ncf1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.21 NCF1 Zornitza Stark edited their review of gene: NCF1: Changed rating: AMBER
BabyScreen+ newborn screening v1.21 HBA1 Zornitza Stark Tag for review was removed from gene: HBA1.
Tag treatable tag was added to gene: HBA1.
BabyScreen+ newborn screening v1.21 HBA2 Zornitza Stark Tag for review was removed from gene: HBA2.
Tag technically challenging tag was added to gene: HBA2.
BabyScreen+ newborn screening v1.21 HBA1 Zornitza Stark Tag technically challenging tag was added to gene: HBA1.
BabyScreen+ newborn screening v1.21 IKBKG Zornitza Stark Tag technically challenging tag was added to gene: IKBKG.
BabyScreen+ newborn screening v1.21 IGHM Zornitza Stark Classified gene: IGHM as Green List (high evidence)
BabyScreen+ newborn screening v1.21 IGHM Zornitza Stark Gene: ighm has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.20 IGHM Zornitza Stark changed review comment from: RefSeq annotation issues.; to: RefSeq annotation issues. Specific rescue loop built to capture variants.
BabyScreen+ newborn screening v1.20 IGHM Zornitza Stark edited their review of gene: IGHM: Changed rating: GREEN
BabyScreen+ newborn screening v1.20 NCF1 Zornitza Stark Classified gene: NCF1 as Green List (high evidence)
BabyScreen+ newborn screening v1.20 NCF1 Zornitza Stark Gene: ncf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.19 NCF1 Zornitza Stark edited their review of gene: NCF1: Changed rating: GREEN
BabyScreen+ newborn screening v1.19 NCF1 Zornitza Stark Classified gene: NCF1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v1.19 NCF1 Zornitza Stark Gene: ncf1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.18 NCF1 Zornitza Stark Tag technically challenging tag was added to gene: NCF1.
BabyScreen+ newborn screening v1.18 NCF1 Zornitza Stark edited their review of gene: NCF1: Added comment: Mappability issues.; Changed rating: AMBER
BabyScreen+ newborn screening v1.18 CYP21A2 Zornitza Stark Classified gene: CYP21A2 as Green List (high evidence)
BabyScreen+ newborn screening v1.18 CYP21A2 Zornitza Stark Gene: cyp21a2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v1.17 CYP21A2 Zornitza Stark Tag treatable tag was added to gene: CYP21A2.
Tag endocrine tag was added to gene: CYP21A2.
Tag technically challenging tag was added to gene: CYP21A2.
BabyScreen+ newborn screening v1.17 CYP21A2 Zornitza Stark edited their review of gene: CYP21A2: Added comment: Part of Victorian sNBS, therefore include, although technically challenging.; Changed rating: GREEN
BabyScreen+ newborn screening v1.17 CORO1A Zornitza Stark Tag technically challenging tag was added to gene: CORO1A.
BabyScreen+ newborn screening v1.17 F8 Zornitza Stark Tag for review was removed from gene: F8.
Tag technically challenging tag was added to gene: F8.
BabyScreen+ newborn screening v1.17 GBA Zornitza Stark Tag technically challenging tag was added to gene: GBA.
BabyScreen+ newborn screening v1.17 PMS2 Zornitza Stark Classified gene: PMS2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v1.17 PMS2 Zornitza Stark Gene: pms2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.16 PMS2 Zornitza Stark Tag technically challenging tag was added to gene: PMS2.
BabyScreen+ newborn screening v1.16 PMS2 Zornitza Stark edited their review of gene: PMS2: Added comment: Mappability issues.; Changed rating: AMBER
BabyScreen+ newborn screening v1.16 IGHM Zornitza Stark Classified gene: IGHM as Amber List (moderate evidence)
BabyScreen+ newborn screening v1.16 IGHM Zornitza Stark Gene: ighm has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.15 IGHM Zornitza Stark Tag technically challenging tag was added to gene: IGHM.
BabyScreen+ newborn screening v1.15 IGHM Zornitza Stark edited their review of gene: IGHM: Changed rating: AMBER
BabyScreen+ newborn screening v1.15 IGHM Zornitza Stark commented on gene: IGHM: RefSeq annotation issues.
BabyScreen+ newborn screening v1.15 STRC Zornitza Stark Classified gene: STRC as Amber List (moderate evidence)
BabyScreen+ newborn screening v1.15 STRC Zornitza Stark Gene: strc has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.14 STRC Zornitza Stark Tag technically challenging tag was added to gene: STRC.
BabyScreen+ newborn screening v1.14 STRC Zornitza Stark edited their review of gene: STRC: Added comment: Technical issues with multi-mapping, therefore exclude for now.; Changed rating: AMBER
BabyScreen+ newborn screening v1.14 KCNA5 Zornitza Stark Marked gene: KCNA5 as ready
BabyScreen+ newborn screening v1.14 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.14 KCNA5 Zornitza Stark Phenotypes for gene: KCNA5 were changed from Atrial fibrillation to Atrial fibrillation, familial, 7, MIM# 612240
BabyScreen+ newborn screening v1.13 KCNA5 Zornitza Stark Classified gene: KCNA5 as Red List (low evidence)
BabyScreen+ newborn screening v1.13 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.12 KCNA5 Zornitza Stark reviewed gene: KCNA5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrial fibrillation, familial, 7, MIM# 612240; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Marked gene: GABRG2 as ready
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Classified gene: GABRG2 as Red List (low evidence)
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Classified gene: GABRG2 as Red List (low evidence)
BabyScreen+ newborn screening v1.12 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.11 GABRG2 Zornitza Stark reviewed gene: GABRG2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 74 618396, Epilepsy, generalized, with febrile seizures plus, type 3 607681; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.11 DKC1 Zornitza Stark Marked gene: DKC1 as ready
BabyScreen+ newborn screening v1.11 DKC1 Zornitza Stark Gene: dkc1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.11 DKC1 Zornitza Stark Phenotypes for gene: DKC1 were changed from Dyskeratosis congenita, X-linked, MIM# 305000; Dyskeratosis congenita to Dyskeratosis congenita, X-linked, MIM# 305000
BabyScreen+ newborn screening v1.10 DKC1 Zornitza Stark Classified gene: DKC1 as Red List (low evidence)
BabyScreen+ newborn screening v1.10 DKC1 Zornitza Stark Gene: dkc1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.9 DKC1 Zornitza Stark reviewed gene: DKC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyskeratosis congenita, X-linked, MIM# 305000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v1.9 CDKN2A Zornitza Stark Marked gene: CDKN2A as ready
BabyScreen+ newborn screening v1.9 CDKN2A Zornitza Stark Gene: cdkn2a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.9 CDKN2A Zornitza Stark Phenotypes for gene: CDKN2A were changed from Melanoma to {Melanoma, cutaneous malignant, 2}, MIM# 155601
BabyScreen+ newborn screening v1.8 CDKN2A Zornitza Stark Classified gene: CDKN2A as Red List (low evidence)
BabyScreen+ newborn screening v1.8 CDKN2A Zornitza Stark Gene: cdkn2a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.7 CDKN2A Zornitza Stark reviewed gene: CDKN2A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Melanoma, cutaneous malignant, 2}, MIM# 155601; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.7 BMPR2 Zornitza Stark Marked gene: BMPR2 as ready
BabyScreen+ newborn screening v1.7 BMPR2 Zornitza Stark Gene: bmpr2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.7 BMPR2 Zornitza Stark Phenotypes for gene: BMPR2 were changed from Pulmonary hypertension, familial primary to Pulmonary hypertension, familial primary, 1, with or without HHT, MIM# 178600
BabyScreen+ newborn screening v1.6 BMPR2 Zornitza Stark Classified gene: BMPR2 as Red List (low evidence)
BabyScreen+ newborn screening v1.6 BMPR2 Zornitza Stark Gene: bmpr2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.5 BMPR2 Zornitza Stark reviewed gene: BMPR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, familial primary, 1, with or without HHT, MIM# 178600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.5 AIP Zornitza Stark Classified gene: AIP as Red List (low evidence)
BabyScreen+ newborn screening v1.5 AIP Zornitza Stark Gene: aip has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.4 AIP Zornitza Stark edited their review of gene: AIP: Changed rating: RED
BabyScreen+ newborn screening v1.4 PHOX2B Zornitza Stark Marked gene: PHOX2B as ready
BabyScreen+ newborn screening v1.4 PHOX2B Zornitza Stark Gene: phox2b has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.4 PHOX2B Zornitza Stark Phenotypes for gene: PHOX2B were changed from Central hypoventilation syndrome to Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, MIM# 209880
BabyScreen+ newborn screening v1.3 PHOX2B Zornitza Stark Classified gene: PHOX2B as Red List (low evidence)
BabyScreen+ newborn screening v1.3 PHOX2B Zornitza Stark Gene: phox2b has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v1.2 PHOX2B Zornitza Stark reviewed gene: PHOX2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, MIM# 209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.2 AIP Zornitza Stark Marked gene: AIP as ready
BabyScreen+ newborn screening v1.2 AIP Zornitza Stark Gene: aip has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v1.2 AIP Zornitza Stark Phenotypes for gene: AIP were changed from Pituitary adenoma to Pituitary adenoma predisposition, MIM# 102200
BabyScreen+ newborn screening v1.1 AIP Zornitza Stark reviewed gene: AIP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary adenoma predisposition, MIM# 102200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v1.1 UMPS Zornitza Stark Tag for review was removed from gene: UMPS.
BabyScreen+ newborn screening v1.1 SMN1 Zornitza Stark Tag for review was removed from gene: SMN1.
BabyScreen+ newborn screening v1.1 OAT Zornitza Stark Tag for review was removed from gene: OAT.
BabyScreen+ newborn screening v1.1 MLH1 Zornitza Stark Tag for review was removed from gene: MLH1.
BabyScreen+ newborn screening v1.1 KCNJ2 Zornitza Stark Tag for review was removed from gene: KCNJ2.
Tag treatable tag was added to gene: KCNJ2.
BabyScreen+ newborn screening v1.1 HIBCH Zornitza Stark Tag for review was removed from gene: HIBCH.
BabyScreen+ newborn screening v1.1 NIPAL4 Zornitza Stark Tag for review was removed from gene: NIPAL4.
Tag treatable tag was added to gene: NIPAL4.
Tag dermatological tag was added to gene: NIPAL4.
BabyScreen+ newborn screening v1.1 SAMD9 Zornitza Stark Tag treatable tag was added to gene: SAMD9.
Tag endocrine tag was added to gene: SAMD9.
Tag haematological tag was added to gene: SAMD9.
BabyScreen+ newborn screening v1.1 PDP1 Zornitza Stark Tag treatable tag was added to gene: PDP1.
Tag metabolic tag was added to gene: PDP1.
BabyScreen+ newborn screening v1.1 GFI1 Zornitza Stark Tag treatable tag was added to gene: GFI1.
Tag immunological tag was added to gene: GFI1.
BabyScreen+ newborn screening v1.1 DLAT Zornitza Stark Tag treatable tag was added to gene: DLAT.
Tag metabolic tag was added to gene: DLAT.
BabyScreen+ newborn screening v1.1 CORO1A Zornitza Stark Tag treatable tag was added to gene: CORO1A.
Tag immunological tag was added to gene: CORO1A.
BabyScreen+ newborn screening v1.1 CD70 Zornitza Stark Tag treatable tag was added to gene: CD70.
Tag immunological tag was added to gene: CD70.
BabyScreen+ newborn screening v1.1 CD40 Zornitza Stark Tag treatable tag was added to gene: CD40.
Tag immunological tag was added to gene: CD40.
BabyScreen+ newborn screening v1.1 BMP1 Zornitza Stark Tag skeletal tag was added to gene: BMP1.
BabyScreen+ newborn screening v1.1 Zornitza Stark Panel name changed from Baby Screen+ newborn screening to BabyScreen+ newborn screening
BabyScreen+ newborn screening v1.0 Zornitza Stark promoted panel to version 1.0
BabyScreen+ newborn screening v0.2180 KCNQ1 Zornitza Stark Phenotypes for gene: KCNQ1 were changed from Long QT syndrome 1, MIM# 192500 to Jervell and Lange-Nielsen syndrome MIM#220400; Long QT syndrome 1, MIM# 192500
BabyScreen+ newborn screening v0.2179 KCNQ1 Zornitza Stark Mode of inheritance for gene: KCNQ1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2178 KCNQ1 Zornitza Stark Tag deafness tag was added to gene: KCNQ1.
BabyScreen+ newborn screening v0.2178 DMD Zornitza Stark Classified gene: DMD as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2178 DMD Zornitza Stark Gene: dmd has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2177 DMD Zornitza Stark Tag for review was removed from gene: DMD.
BabyScreen+ newborn screening v0.2177 DMD Zornitza Stark edited their review of gene: DMD: Added comment: Reviewed with RCH Neurology team: treatments currently not approved by the TGA. Downgrade to Amber, can be upgraded when this changes.; Changed rating: AMBER
BabyScreen+ newborn screening v0.2177 KCNQ1 Lilian Downie reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301579; Phenotypes: Jervell and Lange-Nielsen syndrome MIM#220400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2177 PLG Zornitza Stark Mode of inheritance for gene: PLG was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2176 ABCD4 Zornitza Stark Tag metabolic tag was added to gene: ABCD4.
BabyScreen+ newborn screening v0.2176 COL4A6 Zornitza Stark Classified gene: COL4A6 as Red List (low evidence)
BabyScreen+ newborn screening v0.2176 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2175 COL4A6 Zornitza Stark edited their review of gene: COL4A6: Added comment: Further review of PMID:33840813;

Family A:
- Proband is hemi for COL4A6 and het for GJB2. Mother is het for COL4A6
- hypothesised that in the proband is more severe than the parents due to additive effects of his two variants however, mother's audiometric data was unavailable to confirm this.

Family B:
- Variant does not segregate within family with the proband being WT in this gene
- NM_001287758.1: c.3272G>C is the mutation however, it appears to be an annotation error as it corresponds to NC_000023.11:g.108171443 in GRCh38. At that position, the c. is T not G and the amino acid residue is Val, not Gly.

In addition, there is a missense affecting Gly of GXY in gnomad v3 with 38 hemis.; Changed rating: RED; Changed publications: 33840813; Changed phenotypes: Deafness, X-linked 6 MIM#300914; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.2175 MT-RNR1 Zornitza Stark changed review comment from: The following variants have been associated with aminoglycoside-induced deafness:
m.1555A>G
m.1005T>C
m.1095T>C

Alerts can be placed in medical records to avoid aminoglycoside administration.
Sources: Expert Review; to: The following variants have been associated with aminoglycoside-induced deafness:
m.1555A>G and m.1494C>T

Alerts can be placed in medical records to avoid aminoglycoside administration.
Sources: Expert Review
BabyScreen+ newborn screening v0.2175 PDP1 Zornitza Stark Marked gene: PDP1 as ready
BabyScreen+ newborn screening v0.2175 PDP1 Zornitza Stark Gene: pdp1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2175 PDP1 Zornitza Stark Phenotypes for gene: PDP1 were changed from Pyruvate dehydrogenase phosphatase deficiency to Pyruvate dehydrogenase phosphatase deficiency, MIM# 608782
BabyScreen+ newborn screening v0.2174 PDP1 Zornitza Stark Classified gene: PDP1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2174 PDP1 Zornitza Stark Gene: pdp1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2174 PDP1 Zornitza Stark Classified gene: PDP1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2174 PDP1 Zornitza Stark Gene: pdp1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2173 PDP1 Zornitza Stark reviewed gene: PDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pyruvate dehydrogenase phosphatase deficiency, MIM# 608782; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2173 DLAT Zornitza Stark Marked gene: DLAT as ready
BabyScreen+ newborn screening v0.2173 DLAT Zornitza Stark Gene: dlat has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2173 DLAT Zornitza Stark Classified gene: DLAT as Green List (high evidence)
BabyScreen+ newborn screening v0.2173 DLAT Zornitza Stark Gene: dlat has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2172 DLAT Zornitza Stark gene: DLAT was added
gene: DLAT was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: DLAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DLAT were set to Pyruvate dehydrogenase E2 deficiency, MIM# 245348
Review for gene: DLAT was set to GREEN
Added comment: Well established gene-disease association.

Clinical presentation is in infancy.

Treatment: ketogenic diet has a significant impact on outcome; some cases responsive to thiamine

Non-genetic confirmatory testing: enzymology

Included for consistency with PDHA1/PDHX
Sources: Expert Review
BabyScreen+ newborn screening v0.2171 PDHB Zornitza Stark Marked gene: PDHB as ready
BabyScreen+ newborn screening v0.2171 PDHB Zornitza Stark Gene: pdhb has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2171 PDHB Zornitza Stark Classified gene: PDHB as Green List (high evidence)
BabyScreen+ newborn screening v0.2171 PDHB Zornitza Stark Gene: pdhb has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2170 PDHB Zornitza Stark gene: PDHB was added
gene: PDHB was added to Baby Screen+ newborn screening. Sources: Expert Review
treatable, metabolic tags were added to gene: PDHB.
Mode of inheritance for gene: PDHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDHB were set to Pyruvate dehydrogenase E1-beta deficiency, MIM# 614111
Review for gene: PDHB was set to GREEN
Added comment: Well established gene-disease association.

Clinical presentation is in infancy.

Treatment: ketogenic diet has a significant impact on outcome; some cases responsive to thiamine

Non-genetic confirmatory testing: enzymology

Included for consistency with PDHA1/PDHX
Sources: Expert Review
BabyScreen+ newborn screening v0.2169 TUBB4B Zornitza Stark Marked gene: TUBB4B as ready
BabyScreen+ newborn screening v0.2169 TUBB4B Zornitza Stark Gene: tubb4b has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2169 TUBB4B Zornitza Stark Classified gene: TUBB4B as Red List (low evidence)
BabyScreen+ newborn screening v0.2169 TUBB4B Zornitza Stark Gene: tubb4b has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2168 SUFU Zornitza Stark Marked gene: SUFU as ready
BabyScreen+ newborn screening v0.2168 SUFU Zornitza Stark Gene: sufu has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2168 SUFU Zornitza Stark Classified gene: SUFU as Red List (low evidence)
BabyScreen+ newborn screening v0.2168 SUFU Zornitza Stark Gene: sufu has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2167 SLITRK6 Zornitza Stark Marked gene: SLITRK6 as ready
BabyScreen+ newborn screening v0.2167 SLITRK6 Zornitza Stark Gene: slitrk6 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2167 SLITRK6 Zornitza Stark Tag deafness tag was added to gene: SLITRK6.
BabyScreen+ newborn screening v0.2167 SLITRK6 Zornitza Stark Classified gene: SLITRK6 as Green List (high evidence)
BabyScreen+ newborn screening v0.2167 SLITRK6 Zornitza Stark Gene: slitrk6 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2166 PAX5 Zornitza Stark Marked gene: PAX5 as ready
BabyScreen+ newborn screening v0.2166 PAX5 Zornitza Stark Gene: pax5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2166 PAX5 Zornitza Stark Classified gene: PAX5 as Red List (low evidence)
BabyScreen+ newborn screening v0.2166 PAX5 Zornitza Stark Gene: pax5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2165 GREB1L Zornitza Stark Tag deafness tag was added to gene: GREB1L.
BabyScreen+ newborn screening v0.2165 MPZL2 Zornitza Stark Marked gene: MPZL2 as ready
BabyScreen+ newborn screening v0.2165 MPZL2 Zornitza Stark Gene: mpzl2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2165 MPZL2 Zornitza Stark Classified gene: MPZL2 as Red List (low evidence)
BabyScreen+ newborn screening v0.2165 MPZL2 Zornitza Stark Gene: mpzl2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2164 LMX1A Zornitza Stark Marked gene: LMX1A as ready
BabyScreen+ newborn screening v0.2164 LMX1A Zornitza Stark Gene: lmx1a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2164 LMX1A Zornitza Stark Classified gene: LMX1A as Red List (low evidence)
BabyScreen+ newborn screening v0.2164 LMX1A Zornitza Stark Gene: lmx1a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2163 GREB1L Zornitza Stark Marked gene: GREB1L as ready
BabyScreen+ newborn screening v0.2163 GREB1L Zornitza Stark Gene: greb1l has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2163 GREB1L Zornitza Stark Classified gene: GREB1L as Green List (high evidence)
BabyScreen+ newborn screening v0.2163 GREB1L Zornitza Stark Gene: greb1l has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2162 NLRP3 Zornitza Stark Marked gene: NLRP3 as ready
BabyScreen+ newborn screening v0.2162 NLRP3 Zornitza Stark Gene: nlrp3 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2162 NLRP3 Zornitza Stark Classified gene: NLRP3 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2162 NLRP3 Zornitza Stark Gene: nlrp3 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2161 NLRP3 Zornitza Stark Tag treatable tag was added to gene: NLRP3.
Tag immunological tag was added to gene: NLRP3.
BabyScreen+ newborn screening v0.2161 NLRP3 Zornitza Stark gene: NLRP3 was added
gene: NLRP3 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: NLRP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NLRP3 were set to 25038238
Phenotypes for gene: NLRP3 were set to Familial cold inflammatory syndrome 1, MIM#120100 Muckle-Wells syndrome, MIM#191900 CINCA syndrome, MIM#607115 Deafness, autosomal dominant 34, with or without inflammation, MIM#617772 Keratoendothelitis fugax hereditaria, MIM#148200
Review for gene: NLRP3 was set to AMBER
Added comment: Established gene-disease associations.

Variants in this gene cause a spectrum of clinical phenotypes, ranging from onset in infancy to adult-onset, with variable severity. Genotype-phenotype correlation is unclear, hence not suitable for inclusion at this time.

Treatment: corticosteroids, anakinra, rilonacept and canakinumab.

Non-genetic confirmatory testing: no.
Sources: Expert Review
BabyScreen+ newborn screening v0.2160 AMT Zornitza Stark Tag treatable tag was added to gene: AMT.
Tag metabolic tag was added to gene: AMT.
BabyScreen+ newborn screening v0.2160 AMT Zornitza Stark Publications for gene: AMT were set to
BabyScreen+ newborn screening v0.2159 AMT Zornitza Stark Classified gene: AMT as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2159 AMT Zornitza Stark Gene: amt has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2158 AMT Zornitza Stark edited their review of gene: AMT: Added comment: Severe infantile forms: treatment does not currently alter outcomes.

Attenuated forms can have onset in childhood, therapy with sodium benzoate and NMDA (The N-methyl-D-aspartate receptor) receptor site antagonists (dextromethorphan, ketamine) but uncertainty about effectiveness.; Changed rating: AMBER; Changed publications: 35683414
BabyScreen+ newborn screening v0.2158 GLDC Zornitza Stark Publications for gene: GLDC were set to 16404748; 34513771
BabyScreen+ newborn screening v0.2157 GLDC Zornitza Stark Classified gene: GLDC as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2157 GLDC Zornitza Stark Gene: gldc has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2156 GLDC Zornitza Stark changed review comment from: Severe form likely to present clinically, so milder forms, which are more amenable to treatment are likely to be identified through screening.; to: Severe form likely to present clinically, so milder forms, which are more amenable to treatment are likely to be identified through screening.

However, the effectiveness of treatment is not established, PMID 35683414 for a recent review.
BabyScreen+ newborn screening v0.2156 GLDC Zornitza Stark edited their review of gene: GLDC: Changed rating: AMBER; Changed publications: 35683414
BabyScreen+ newborn screening v0.2156 GLDC Zornitza Stark Classified gene: GLDC as Green List (high evidence)
BabyScreen+ newborn screening v0.2156 GLDC Zornitza Stark Gene: gldc has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2155 GLDC Zornitza Stark commented on gene: GLDC: Severe form likely to present clinically, so milder forms, which are more amenable to treatment are likely to be identified through screening.
BabyScreen+ newborn screening v0.2155 SAMHD1 Zornitza Stark Classified gene: SAMHD1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2155 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2154 SAMHD1 Zornitza Stark reviewed gene: SAMHD1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2154 CYP27A1 Zornitza Stark Tag for review was removed from gene: CYP27A1.
Tag metabolic tag was added to gene: CYP27A1.
BabyScreen+ newborn screening v0.2154 CYP27A1 Zornitza Stark Classified gene: CYP27A1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2154 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2153 CYP27A1 Zornitza Stark edited their review of gene: CYP27A1: Added comment: Average age of onset is in late childhood, but a proportion would have onset < 5yo and early treatment beneficial.; Changed rating: GREEN; Changed publications: 24442603
BabyScreen+ newborn screening v0.2153 SGSH Zornitza Stark Publications for gene: SGSH were set to
BabyScreen+ newborn screening v0.2152 SGSH Zornitza Stark Classified gene: SGSH as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2152 SGSH Zornitza Stark Gene: sgsh has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2152 SGSH Zornitza Stark Classified gene: SGSH as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2152 SGSH Zornitza Stark Gene: sgsh has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2152 SGSH Zornitza Stark Classified gene: SGSH as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2152 SGSH Zornitza Stark Gene: sgsh has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2151 SGSH Zornitza Stark Tag clinical trial tag was added to gene: SGSH.
BabyScreen+ newborn screening v0.2151 SGSH Zornitza Stark reviewed gene: SGSH: Rating: AMBER; Mode of pathogenicity: None; Publications: 31044143; Phenotypes: Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2151 GPR161 Zornitza Stark Marked gene: GPR161 as ready
BabyScreen+ newborn screening v0.2151 GPR161 Zornitza Stark Gene: gpr161 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2151 GPR161 Zornitza Stark Classified gene: GPR161 as Red List (low evidence)
BabyScreen+ newborn screening v0.2151 GPR161 Zornitza Stark Gene: gpr161 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2150 GPR161 Zornitza Stark Tag cancer tag was added to gene: GPR161.
BabyScreen+ newborn screening v0.2150 CTR9 Zornitza Stark Tag cancer tag was added to gene: CTR9.
BabyScreen+ newborn screening v0.2150 CTR9 Zornitza Stark Marked gene: CTR9 as ready
BabyScreen+ newborn screening v0.2150 CTR9 Zornitza Stark Gene: ctr9 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2150 CTR9 Zornitza Stark Classified gene: CTR9 as Red List (low evidence)
BabyScreen+ newborn screening v0.2150 CTR9 Zornitza Stark Gene: ctr9 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2149 ALK Zornitza Stark Marked gene: ALK as ready
BabyScreen+ newborn screening v0.2149 ALK Zornitza Stark Gene: alk has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2149 ALK Zornitza Stark Tag cancer tag was added to gene: ALK.
BabyScreen+ newborn screening v0.2149 ALK Zornitza Stark Classified gene: ALK as Red List (low evidence)
BabyScreen+ newborn screening v0.2149 ALK Zornitza Stark Gene: alk has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2148 SUFU Lilian Downie gene: SUFU was added
gene: SUFU was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SUFU was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SUFU were set to PMID: 29186568
Phenotypes for gene: SUFU were set to {Medulloblastoma} MIM#155255
Penetrance for gene: SUFU were set to Incomplete
Review for gene: SUFU was set to RED
Added comment: Medullobastoma 1st year of life
incomplete penetrance
worse outcomes
no determined screening protocol
Sources: Expert list
BabyScreen+ newborn screening v0.2148 PAX5 Lilian Downie gene: PAX5 was added
gene: PAX5 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: PAX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAX5 were set to PMID: 24013638
Phenotypes for gene: PAX5 were set to {Leukemia, acute lymphoblastic, susceptibility to, 3} MIM#615545
Penetrance for gene: PAX5 were set to Incomplete
Review for gene: PAX5 was set to RED
Added comment: Incomplete penetrance
Sources: Expert list
BabyScreen+ newborn screening v0.2148 GPR161 Lilian Downie gene: GPR161 was added
gene: GPR161 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GPR161 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPR161 were set to PMID: 31609649
Phenotypes for gene: GPR161 were set to Medulloblastoma predisposition syndrome MIM#155255
Penetrance for gene: GPR161 were set to Incomplete
Review for gene: GPR161 was set to RED
Added comment: Increased risk of medulloblastoma at <3yrs
Also identified in population and healthy parents
Sources: Expert list
BabyScreen+ newborn screening v0.2148 CTR9 Lilian Downie gene: CTR9 was added
gene: CTR9 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CTR9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTR9 were set to PMID: 32412586
Phenotypes for gene: CTR9 were set to Wilms tumour predisposition
Penetrance for gene: CTR9 were set to Incomplete
Review for gene: CTR9 was set to RED
Added comment: 9/14 germline variant developed Wilms (in 4 families)
Red due to reduced penetrance
Sources: Expert list
BabyScreen+ newborn screening v0.2148 ALK Lilian Downie gene: ALK was added
gene: ALK was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: ALK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALK were set to PMID: 22071890
Phenotypes for gene: ALK were set to {Neuroblastoma, susceptibility to, 3} MIM#613014
Penetrance for gene: ALK were set to Incomplete
Review for gene: ALK was set to RED
Added comment: Reduced penetrance
Not clear guideline on management if detected
Sources: Expert list
BabyScreen+ newborn screening v0.2148 TUBB4B Lilian Downie gene: TUBB4B was added
gene: TUBB4B was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TUBB4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4B were set to PMID: 29198720, 35240325
Phenotypes for gene: TUBB4B were set to Leber congenital amaurosis with early-onset deafness MIM#617879
Review for gene: TUBB4B was set to RED
Added comment: The TUBB4B gene has been associated with autosomal dominant Leber congenital amaurosis with early-onset deafness
Not consistently hearing phenotype <5years therefore excluded
Sources: Expert list
BabyScreen+ newborn screening v0.2148 SLITRK6 Lilian Downie gene: SLITRK6 was added
gene: SLITRK6 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SLITRK6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLITRK6 were set to PMID: 23543054, PMID: 25590127
Phenotypes for gene: SLITRK6 were set to Deafness and myopia MIM#221200
Review for gene: SLITRK6 was set to GREEN
Added comment: Congenital or prelingual deafness (SNHL or ANSD)
high myopia
Sources: Expert list
BabyScreen+ newborn screening v0.2148 MPZL2 Lilian Downie gene: MPZL2 was added
gene: MPZL2 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: MPZL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPZL2 were set to PMID: 29982980, 29961571, 35734045,33234333
Phenotypes for gene: MPZL2 were set to Deafness, autosomal recessive 111 MIM#618145
Review for gene: MPZL2 was set to RED
Added comment: Most cases are pre-lingual but 29961571, 35734045 report adult onset so I think should be excluded based on variability of age of onset
Sources: Expert list
BabyScreen+ newborn screening v0.2148 CRYM Zornitza Stark Marked gene: CRYM as ready
BabyScreen+ newborn screening v0.2148 CRYM Zornitza Stark Gene: crym has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2148 CRYM Zornitza Stark Classified gene: CRYM as Red List (low evidence)
BabyScreen+ newborn screening v0.2148 CRYM Zornitza Stark Gene: crym has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2147 COL4A6 Zornitza Stark Marked gene: COL4A6 as ready
BabyScreen+ newborn screening v0.2147 COL4A6 Zornitza Stark Added comment: Comment when marking as ready: Agree, report in males only.
BabyScreen+ newborn screening v0.2147 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2147 COL4A6 Zornitza Stark Classified gene: COL4A6 as Green List (high evidence)
BabyScreen+ newborn screening v0.2147 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2146 CLDN9 Zornitza Stark Marked gene: CLDN9 as ready
BabyScreen+ newborn screening v0.2146 CLDN9 Zornitza Stark Gene: cldn9 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2146 CLDN9 Zornitza Stark Classified gene: CLDN9 as Red List (low evidence)
BabyScreen+ newborn screening v0.2146 CLDN9 Zornitza Stark Gene: cldn9 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2145 CEP250 Zornitza Stark Marked gene: CEP250 as ready
BabyScreen+ newborn screening v0.2145 CEP250 Zornitza Stark Gene: cep250 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2145 CEP250 Zornitza Stark Classified gene: CEP250 as Red List (low evidence)
BabyScreen+ newborn screening v0.2145 CEP250 Zornitza Stark Gene: cep250 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2144 ABHD12 Zornitza Stark Marked gene: ABHD12 as ready
BabyScreen+ newborn screening v0.2144 ABHD12 Zornitza Stark Gene: abhd12 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2144 ABHD12 Zornitza Stark Classified gene: ABHD12 as Red List (low evidence)
BabyScreen+ newborn screening v0.2144 ABHD12 Zornitza Stark Gene: abhd12 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2143 CD164 Zornitza Stark Marked gene: CD164 as ready
BabyScreen+ newborn screening v0.2143 CD164 Zornitza Stark Gene: cd164 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2143 CD164 Zornitza Stark Classified gene: CD164 as Red List (low evidence)
BabyScreen+ newborn screening v0.2143 CD164 Zornitza Stark Gene: cd164 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2142 AP1B1 Zornitza Stark Marked gene: AP1B1 as ready
BabyScreen+ newborn screening v0.2142 AP1B1 Zornitza Stark Gene: ap1b1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2142 AP1B1 Zornitza Stark Classified gene: AP1B1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2142 AP1B1 Zornitza Stark Gene: ap1b1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2141 AP1B1 Zornitza Stark reviewed gene: AP1B1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Keratitis-ichthyosis-deafness syndrome, autosomal recessive MIM#242150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2141 LMX1A Lilian Downie gene: LMX1A was added
gene: LMX1A was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: LMX1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMX1A were set to PMID: 29754270
Phenotypes for gene: LMX1A were set to Deafness, autosomal dominant 7 MIM#601412
Review for gene: LMX1A was set to RED
Added comment: Age of onset too variable
Sources: Expert list
BabyScreen+ newborn screening v0.2141 GREB1L Lilian Downie gene: GREB1L was added
gene: GREB1L was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GREB1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GREB1L were set to PMID: 29955957, 32585897
Phenotypes for gene: GREB1L were set to Deafness, autosomal dominant 80 MIM#619274
Review for gene: GREB1L was set to GREEN
Added comment: Congenital hearing impairment with cochlear abnormalities
This gene also causes Renal hypodysplasia/aplasia 3 MIM#617805 with no clear difference in mutation spectrum
Sources: Expert list
BabyScreen+ newborn screening v0.2141 CRYM Lilian Downie gene: CRYM was added
gene: CRYM was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CRYM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRYM were set to PMID: 12471561, 32742378
Phenotypes for gene: CRYM were set to Deafness, autosomal dominant 40 MIM#616357
Review for gene: CRYM was set to RED
Added comment: Dominant hearing loss
One paper infant onset, the other all adult onset
Sources: Expert list
BabyScreen+ newborn screening v0.2141 COL4A6 Lilian Downie gene: COL4A6 was added
gene: COL4A6 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: COL4A6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: COL4A6 were set to PMID: 33840813, PMID: 23714752
Phenotypes for gene: COL4A6 were set to Deafness, X-linked 6 MIM#300914
Review for gene: COL4A6 was set to GREEN
Added comment: Pre-lingual or congenital deafness in males
consider not reporting in females (may have adult onset hearing impairment)
Sources: Expert list
BabyScreen+ newborn screening v0.2141 CLDN9 Lilian Downie gene: CLDN9 was added
gene: CLDN9 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CLDN9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLDN9 were set to PMID: 34265170
Phenotypes for gene: CLDN9 were set to Deafness, autosomal recessive 116 MIM#619093
Review for gene: CLDN9 was set to RED
Added comment: Age of onset not consistently <5
Sources: Expert list
BabyScreen+ newborn screening v0.2141 CEP250 Lilian Downie gene: CEP250 was added
gene: CEP250 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CEP250 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP250 were set to PMID: 34223797, PMID: 29718797, PMID: 30459346, PMID: 28005958
Phenotypes for gene: CEP250 were set to Cone-rod dystrophy and hearing loss 2 MIM#618358
Review for gene: CEP250 was set to RED
Added comment: Hearing loss and RP
Atypical Usher phenotype
Age of onset and penetrance of hearing loss component is variable and seeing as this is the treatable component have excluded from list
Sources: Expert list
BabyScreen+ newborn screening v0.2141 ABHD12 Lilian Downie gene: ABHD12 was added
gene: ABHD12 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: ABHD12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ABHD12 were set to Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract MIM#612674
Review for gene: ABHD12 was set to RED
Added comment: Age of onset not consistently under 5 for treatable elements such as hearing loss.
Sources: Expert list
BabyScreen+ newborn screening v0.2141 CD164 Lilian Downie gene: CD164 was added
gene: CD164 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CD164 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CD164 were set to Deafness, autosomal dominant 66 MIM#616969
Review for gene: CD164 was set to RED
Added comment: Green in our mendeliome/deafness but limited evidence by clingen
variable age of onset from newborn to 20's reason for exclusion
Sources: Expert list
BabyScreen+ newborn screening v0.2141 AP1B1 Lilian Downie gene: AP1B1 was added
gene: AP1B1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: AP1B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1B1 were set to PMID:31630791, 31630788, 33452671
Phenotypes for gene: AP1B1 were set to Keratitis-ichthyosis-deafness syndrome, autosomal recessive MIM#242150
Review for gene: AP1B1 was set to GREEN
Added comment: Icthyosis
progressive hearing loss (childhood) often detected newborn screening
photophobia
corneal scarring/keratitis
variable dev delay
part of copper metabolism pathway but no proven treatment
Sources: Expert list
BabyScreen+ newborn screening v0.2141 LAMP2 Zornitza Stark Classified gene: LAMP2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2141 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2140 LAMP2 Zornitza Stark edited their review of gene: LAMP2: Added comment: Treatment is currently symptomatic.

On watch list with regards to specific treatment/clinical trials.; Changed rating: AMBER
BabyScreen+ newborn screening v0.2140 NKX2-5 Zornitza Stark Tag treatable tag was added to gene: NKX2-5.
BabyScreen+ newborn screening v0.2140 MYH7 Zornitza Stark Phenotypes for gene: MYH7 were changed from Laing early-onset distal myopathy, MONDO:0008050; Cardiomyopathy, hypertrophic, 1, OMIM:192600; Dilated cardiomyopathy 1S, MONDO:0013262; Hypertrophic cardiomyopathy 1, MONDO:0008647; Laing distal myopathy, OMIM:160500; Left ventricular noncompaction 5, OMIM:613426; Cardiomyopathy, dilated, 1S, OMIM:613426 to Cardiomyopathy, hypertrophic, 1, MIM# 192600
BabyScreen+ newborn screening v0.2139 MYH7 Zornitza Stark Mode of inheritance for gene: MYH7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2138 MYH7 Zornitza Stark Classified gene: MYH7 as Green List (high evidence)
BabyScreen+ newborn screening v0.2138 MYH7 Zornitza Stark Gene: myh7 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2137 MYH7 Zornitza Stark Tag cardiac tag was added to gene: MYH7.
Tag treatable tag was added to gene: MYH7.
BabyScreen+ newborn screening v0.2137 MYH7 Zornitza Stark edited their review of gene: MYH7: Added comment: Discussed with paedric cardiologist: include bi-allelic cardiac variants as can present in the neonatal period with an aggressive cardiomyopathy and associated arrhythmias.; Changed rating: GREEN; Changed phenotypes: Cardiomyopathy, hypertrophic, 1, MIM# 192600; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2137 KCNJ2 Zornitza Stark Phenotypes for gene: KCNJ2 were changed from Andersen syndrome MIM#170390; Atrial fibrillation, familial, 9 MIM#613980; Short QT syndrome 3 MIM#609622 to Andersen syndrome MIM#170390
BabyScreen+ newborn screening v0.2136 KCNJ2 Zornitza Stark Classified gene: KCNJ2 as Green List (high evidence)
BabyScreen+ newborn screening v0.2136 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2135 KCNJ2 Zornitza Stark edited their review of gene: KCNJ2: Added comment: Include for Andersen syndrome and Long QT-associated variants only. Onset in infancy.; Changed rating: GREEN; Changed phenotypes: Andersen syndrome MIM#170390
BabyScreen+ newborn screening v0.2135 TRDN Zornitza Stark Classified gene: TRDN as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2135 TRDN Zornitza Stark Gene: trdn has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2134 TRDN Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with paediatric cardiologist: variable penetrance and age of onset, does not fulfil criteria for gNBS.
BabyScreen+ newborn screening v0.2134 TRDN Zornitza Stark edited their review of gene: TRDN: Changed rating: AMBER
BabyScreen+ newborn screening v0.2134 TECRL Zornitza Stark Classified gene: TECRL as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2134 TECRL Zornitza Stark Gene: tecrl has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2133 TECRL Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with a paediatric cardiologist: variable penetrance and age of onset, does not fulfil criteria for gNBS.
BabyScreen+ newborn screening v0.2133 TECRL Zornitza Stark edited their review of gene: TECRL: Changed rating: AMBER; Changed phenotypes: Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021
BabyScreen+ newborn screening v0.2133 SCN5A Zornitza Stark Classified gene: SCN5A as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2133 SCN5A Zornitza Stark Gene: scn5a has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2132 SCN5A Zornitza Stark changed review comment from: These two associations have been rated as 'strong actionability' in paediatric patients by ClinGen.

Note LongQT generally has symptom onset in adolescence and Brugada typically presents in adulthood.

For review: age of onset and penetrance.; to: These two associations have been rated as 'strong actionability' in paediatric patients by ClinGen.

Note LongQT generally has symptom onset in adolescence and Brugada typically presents in adulthood.

Reviewed with paediatric cardiologist: generally later age of onset, does not fulfil criteria for gNBS.
BabyScreen+ newborn screening v0.2132 SCN5A Zornitza Stark edited their review of gene: SCN5A: Changed rating: AMBER
BabyScreen+ newborn screening v0.2132 PRKG1 Zornitza Stark Classified gene: PRKG1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2132 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2131 PRKG1 Zornitza Stark changed review comment from: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 31 individuals with PRKG1 pathogenic variants indicated that 63% presented with an aortic dissection and 37% had aortic root enlargement. The cumulative risk of an aortic dissection or repair of an aortic aneurysm by age 55 has been estimated as 86% (95% CI: 70-95%).
Sources: ClinGen; to: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 31 individuals with PRKG1 pathogenic variants indicated that 63% presented with an aortic dissection and 37% had aortic root enlargement. The cumulative risk of an aortic dissection or repair of an aortic aneurysm by age 55 has been estimated as 86% (95% CI: 70-95%).

Discussed with a paediatric cardiologist: variable penetrance and age of onset, does not fulfil criteria for gNBS.
Sources: ClinGen
BabyScreen+ newborn screening v0.2131 PRKG1 Zornitza Stark edited their review of gene: PRKG1: Changed rating: AMBER
BabyScreen+ newborn screening v0.2131 MYH11 Zornitza Stark Classified gene: MYH11 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2131 MYH11 Zornitza Stark Gene: myh11 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2130 MYH11 Zornitza Stark changed review comment from: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 12 individuals with MYH11 pathogenic variants indicated that 34% had an aortic dissection and one individual (8%) underwent prophylactic aortic aneurysm repair.; to: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 12 individuals with MYH11 pathogenic variants indicated that 34% had an aortic dissection and one individual (8%) underwent prophylactic aortic aneurysm repair.

Reviewed with a paediatric cardiologist: variable penetrance and age of onset, does not meet criteria for gNBS.
BabyScreen+ newborn screening v0.2130 MYH11 Zornitza Stark edited their review of gene: MYH11: Changed rating: AMBER
BabyScreen+ newborn screening v0.2130 LOX Zornitza Stark Classified gene: LOX as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2130 LOX Zornitza Stark Gene: lox has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2129 LOX Zornitza Stark changed review comment from: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection.
Sources: ClinGen; to: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection.

Discussed with paediatric cardiologist: variable penetrance and age of onset, does not fit with criteria for gNBS.
Sources: ClinGen
BabyScreen+ newborn screening v0.2129 LOX Zornitza Stark edited their review of gene: LOX: Changed rating: AMBER
BabyScreen+ newborn screening v0.2129 JUP Zornitza Stark Classified gene: JUP as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2129 JUP Zornitza Stark Gene: jup has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2128 JUP Zornitza Stark changed review comment from: Screen for bi-allelic disease as can be earlier onset, more severe.; to: Discussed potentially just screening for bi-allelic disease as can be earlier onset, more severe.

Discussed further with a paediatric cardiologist: variable age of onset and penetrance, therefore does not meet criteria.
BabyScreen+ newborn screening v0.2128 JUP Zornitza Stark edited their review of gene: JUP: Changed rating: AMBER
BabyScreen+ newborn screening v0.2128 DSP Zornitza Stark Classified gene: DSP as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2128 DSP Zornitza Stark Gene: dsp has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2127 DSP Zornitza Stark changed review comment from: Screen for bi-allelic disease as can be more severe, earlier onset.; to: Discussed screening for bi-allelic disease as can be more severe, earlier onset.

Also discussed with paediatric cardiologist: variable age of onset and penetrance, exclude.
BabyScreen+ newborn screening v0.2127 DSP Zornitza Stark edited their review of gene: DSP: Changed rating: AMBER
BabyScreen+ newborn screening v0.2127 CASQ2 Zornitza Stark Classified gene: CASQ2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2127 CASQ2 Zornitza Stark Gene: casq2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2126 CASQ2 Zornitza Stark changed review comment from: Well established gene-disease association.

ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

; to: Well established gene-disease association.

ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Reviewed with paediatric cardiologist: variable penetrance and age of onset.
BabyScreen+ newborn screening v0.2126 CASQ2 Zornitza Stark edited their review of gene: CASQ2: Changed rating: AMBER
BabyScreen+ newborn screening v0.2126 CALM1 Zornitza Stark Classified gene: CALM1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2126 CALM1 Zornitza Stark Gene: calm1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2125 CALM3 Zornitza Stark Phenotypes for gene: CALM3 were changed from Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM# 618782; Long QT syndrome 16, MIM#618782 to Long QT syndrome 16, MIM#618782
BabyScreen+ newborn screening v0.2124 CALM3 Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Exclude for CPVT: association has moderate evidence, there are issues with penetrance, and treatment is generally only recommended in symptomatic individuals.
Sources: ClinGen
BabyScreen+ newborn screening v0.2124 CALM3 Zornitza Stark edited their review of gene: CALM3: Changed phenotypes: Long QT syndrome 16, MIM#618782
BabyScreen+ newborn screening v0.2124 CALM3 Zornitza Stark edited their review of gene: CALM3: Changed rating: GREEN
BabyScreen+ newborn screening v0.2124 CALM3 Zornitza Stark edited their review of gene: CALM3: Changed rating: AMBER
BabyScreen+ newborn screening v0.2124 CALM2 Zornitza Stark Classified gene: CALM2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2124 CALM2 Zornitza Stark Gene: calm2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2123 CALM2 Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with paediatric cardiologist: not for inclusion due to issues with penetrance, plus guidelines only generally recommend treatment is symptomatic individuals.
BabyScreen+ newborn screening v0.2123 CALM2 Zornitza Stark edited their review of gene: CALM2: Changed rating: AMBER
BabyScreen+ newborn screening v0.2123 CALM1 Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with paediatric cardiologist: not for inclusion due to issues with penetrance, plus guidelines only generally recommend treatment is symptomatic individuals.
BabyScreen+ newborn screening v0.2123 CALM1 Zornitza Stark edited their review of gene: CALM1: Changed rating: AMBER
BabyScreen+ newborn screening v0.2123 VAMP1 Zornitza Stark Marked gene: VAMP1 as ready
BabyScreen+ newborn screening v0.2123 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2123 VAMP1 Zornitza Stark Phenotypes for gene: VAMP1 were changed from Spastic ataxia; Myasthenic syndrome, congenital, 25, MIM# 618323 to Myasthenic syndrome, congenital, 25, MIM# 618323
BabyScreen+ newborn screening v0.2122 VAMP1 Zornitza Stark Publications for gene: VAMP1 were set to
BabyScreen+ newborn screening v0.2121 VAMP1 Zornitza Stark Mode of inheritance for gene: VAMP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2120 VAMP1 Zornitza Stark Classified gene: VAMP1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2120 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2119 VAMP1 Zornitza Stark Tag treatable tag was added to gene: VAMP1.
Tag neurological tag was added to gene: VAMP1.
BabyScreen+ newborn screening v0.2119 VAMP1 Zornitza Stark reviewed gene: VAMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28168212, 28253535, 28600779, 17102983; Phenotypes: Myasthenic syndrome, congenital, 25, MIM# 618323; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2119 TUBB1 Zornitza Stark Marked gene: TUBB1 as ready
BabyScreen+ newborn screening v0.2119 TUBB1 Zornitza Stark Gene: tubb1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2119 TUBB1 Zornitza Stark Classified gene: TUBB1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2119 TUBB1 Zornitza Stark Gene: tubb1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2118 TUBB1 Zornitza Stark Tag treatable tag was added to gene: TUBB1.
Tag endocrine tag was added to gene: TUBB1.
BabyScreen+ newborn screening v0.2118 TUBB1 Zornitza Stark gene: TUBB1 was added
gene: TUBB1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TUBB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB1 were set to 30446499
Phenotypes for gene: TUBB1 were set to Congenital hypothyroidism, MONDO:0018612, TUBB1-related; Macrothrombocytopenia, autosomal dominant, TUBB1-related, OMIM # 613112
Review for gene: TUBB1 was set to GREEN
Added comment: At least 3 families reported with congenital hypothyroidism associated with TUBB1 variants. Platelet abnormalities reported.

Treatment: thyroxine.

Non-genetic confirmatory testing: TFTs, blood film.
Sources: Expert list
BabyScreen+ newborn screening v0.2117 SLC26A7 Zornitza Stark Marked gene: SLC26A7 as ready
BabyScreen+ newborn screening v0.2117 SLC26A7 Zornitza Stark Gene: slc26a7 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2117 SLC26A7 Zornitza Stark Classified gene: SLC26A7 as Green List (high evidence)
BabyScreen+ newborn screening v0.2117 SLC26A7 Zornitza Stark Gene: slc26a7 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2116 SLC26A7 Zornitza Stark gene: SLC26A7 was added
gene: SLC26A7 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: SLC26A7.
Mode of inheritance for gene: SLC26A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC26A7 were set to 34780050; 32486989; 31372509; 30333321
Phenotypes for gene: SLC26A7 were set to Congenital hypothyroidism, MONDO:0018612, SLC26A7-related
Review for gene: SLC26A7 was set to GREEN
Added comment: More than 10 unrelated families reported.

Congenital hypothyroidism.

Treatment: thyroxine.

Should be detected through standard NBS.
Sources: Expert list
BabyScreen+ newborn screening v0.2115 OTX2 Zornitza Stark Marked gene: OTX2 as ready
BabyScreen+ newborn screening v0.2115 OTX2 Zornitza Stark Gene: otx2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2115 OTX2 Zornitza Stark Classified gene: OTX2 as Green List (high evidence)
BabyScreen+ newborn screening v0.2115 OTX2 Zornitza Stark Gene: otx2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2114 OTX2 Zornitza Stark gene: OTX2 was added
gene: OTX2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: OTX2.
Mode of inheritance for gene: OTX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OTX2 were set to 18728160; 35320640; 33950863
Phenotypes for gene: OTX2 were set to Pituitary hormone deficiency, combined, 6, MIM# 613986
Review for gene: OTX2 was set to GREEN
Added comment: Variants in this gene have been associated with pituitary hormone deficiency with or without microphthalmia, including of TSH.

Congenital onset.

Microphthalmia would present clinically in the newborn period. Infants with TSH deficiency should be detected by standard NBS.

Treatment: thyroxine and other hormone replacements.
Sources: Expert list
BabyScreen+ newborn screening v0.2113 HESX1 Zornitza Stark Marked gene: HESX1 as ready
BabyScreen+ newborn screening v0.2113 HESX1 Zornitza Stark Gene: hesx1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2113 HESX1 Zornitza Stark Phenotypes for gene: HESX1 were changed from Septooptic dysplasia, MIM# 182230; Pituitary hypoplasia to Pituitary hormone deficiency, combined, 5, MIM# 182230
BabyScreen+ newborn screening v0.2112 HESX1 Zornitza Stark Mode of inheritance for gene: HESX1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2111 HESX1 Zornitza Stark Classified gene: HESX1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2111 HESX1 Zornitza Stark Gene: hesx1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2110 HESX1 Zornitza Stark Tag treatable tag was added to gene: HESX1.
Tag endocrine tag was added to gene: HESX1.
BabyScreen+ newborn screening v0.2110 HESX1 Zornitza Stark reviewed gene: HESX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 5, MIM# 182230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2110 CDCA8 Zornitza Stark Marked gene: CDCA8 as ready
BabyScreen+ newborn screening v0.2110 CDCA8 Zornitza Stark Gene: cdca8 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2110 CDCA8 Zornitza Stark Classified gene: CDCA8 as Green List (high evidence)
BabyScreen+ newborn screening v0.2110 CDCA8 Zornitza Stark Gene: cdca8 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2109 CDCA8 Zornitza Stark gene: CDCA8 was added
gene: CDCA8 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: CDCA8.
Mode of inheritance for gene: CDCA8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CDCA8 were set to 28025328; 29546359
Phenotypes for gene: CDCA8 were set to Congenital hypothyroidism, MONDO:0018612, CDCA8-related
Review for gene: CDCA8 was set to GREEN
Added comment: 4 families (1 with bilallelic variants [parent affected as HTZ], 3 with monoallelic variants) with functional evidence of variants.

Treatment: thyroxine

Likely to be detected on standard NBS.
Sources: Expert list
BabyScreen+ newborn screening v0.2108 FOXN1 Zornitza Stark Marked gene: FOXN1 as ready
BabyScreen+ newborn screening v0.2108 FOXN1 Zornitza Stark Gene: foxn1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2108 FOXN1 Zornitza Stark Phenotypes for gene: FOXN1 were changed from Congenital alopecia with T-cell immunodeficiency; T-cell immunodeficiency, congenital alopecia, and nail dystrophy , MIM#601705; T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant, MIM# 618806 to T-cell immunodeficiency, congenital alopecia, and nail dystrophy, autosomal recessive MIM# 601705; T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant, MIM#t 618806
BabyScreen+ newborn screening v0.2107 FOXN1 Zornitza Stark Publications for gene: FOXN1 were set to
BabyScreen+ newborn screening v0.2106 FOXN1 Zornitza Stark Mode of inheritance for gene: FOXN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2105 FOXN1 Zornitza Stark Classified gene: FOXN1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2105 FOXN1 Zornitza Stark Gene: foxn1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2104 FOXN1 Zornitza Stark Tag treatable tag was added to gene: FOXN1.
Tag immunological tag was added to gene: FOXN1.
BabyScreen+ newborn screening v0.2104 FOXN1 Zornitza Stark reviewed gene: FOXN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31447097, 18339010, 10206641; Phenotypes: T-cell immunodeficiency, congenital alopecia, and nail dystrophy, autosomal recessive MIM# 601705, T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant, MIM#t 618806; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2104 TMEM38B Zornitza Stark Marked gene: TMEM38B as ready
BabyScreen+ newborn screening v0.2104 TMEM38B Zornitza Stark Gene: tmem38b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2104 TMEM38B Zornitza Stark Classified gene: TMEM38B as Green List (high evidence)
BabyScreen+ newborn screening v0.2104 TMEM38B Zornitza Stark Gene: tmem38b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2103 TMEM38B Zornitza Stark Tag treatable tag was added to gene: TMEM38B.
Tag skeletal tag was added to gene: TMEM38B.
BabyScreen+ newborn screening v0.2103 TMEM38B Zornitza Stark gene: TMEM38B was added
gene: TMEM38B was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TMEM38B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM38B were set to 23054245; 28323974
Phenotypes for gene: TMEM38B were set to Osteogenesis imperfecta, type XIV , MIM#615066
Review for gene: TMEM38B was set to GREEN
Added comment: More than 10 families reported.

Variable severity, onset of fractures generally in infancy.

Treatment: bisphosphanates; improvement in BMD reported.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
BabyScreen+ newborn screening v0.2102 SPARC Zornitza Stark Marked gene: SPARC as ready
BabyScreen+ newborn screening v0.2102 SPARC Zornitza Stark Gene: sparc has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2102 SPARC Zornitza Stark gene: SPARC was added
gene: SPARC was added to Baby Screen+ newborn screening. Sources: Expert list
skeletal tags were added to gene: SPARC.
Mode of inheritance for gene: SPARC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPARC were set to 26027498; 34462290
Phenotypes for gene: SPARC were set to Osteogenesis imperfecta, type XVII, MIM# 616507
Review for gene: SPARC was set to RED
Added comment: Established gene-disease association, 5 families reported.

Onset of fractures in infancy.

Prominent neuromuscular features, MRI brain changes; some with ID.

Treatment: bisphosphanates are generally used in OI but the case reports where these have been used do not seem terribly convincing in terms of response/improvement.

Exclude for now.
Sources: Expert list
BabyScreen+ newborn screening v0.2101 SP7 Zornitza Stark Marked gene: SP7 as ready
BabyScreen+ newborn screening v0.2101 SP7 Zornitza Stark Gene: sp7 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2101 SP7 Zornitza Stark Phenotypes for gene: SP7 were changed from Osteogenesis imperfecta, type XII to Osteogenesis imperfecta, type XII, MIM# 613849
BabyScreen+ newborn screening v0.2100 SP7 Zornitza Stark Publications for gene: SP7 were set to
BabyScreen+ newborn screening v0.2099 SP7 Zornitza Stark Mode of inheritance for gene: SP7 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2098 SP7 Zornitza Stark Classified gene: SP7 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2098 SP7 Zornitza Stark Gene: sp7 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2097 SP7 Zornitza Stark Tag skeletal tag was added to gene: SP7.
BabyScreen+ newborn screening v0.2097 SP7 Zornitza Stark reviewed gene: SP7: Rating: AMBER; Mode of pathogenicity: None; Publications: 36881265; Phenotypes: Osteogenesis imperfecta, type XII, MIM# 613849; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2097 SERPINH1 Zornitza Stark Marked gene: SERPINH1 as ready
BabyScreen+ newborn screening v0.2097 SERPINH1 Zornitza Stark Gene: serpinh1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2097 SERPINH1 Zornitza Stark Classified gene: SERPINH1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2097 SERPINH1 Zornitza Stark Gene: serpinh1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2096 SERPINH1 Zornitza Stark gene: SERPINH1 was added
gene: SERPINH1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, skeletal tags were added to gene: SERPINH1.
Mode of inheritance for gene: SERPINH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINH1 were set to 29520608; 25510505; 33524049
Phenotypes for gene: SERPINH1 were set to Osteogenesis imperfecta, type X, MIM# 613848
Review for gene: SERPINH1 was set to GREEN
Added comment: Established gene-disease association.

Onset of fractures is in infancy.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
BabyScreen+ newborn screening v0.2095 SERPINF1 Zornitza Stark Marked gene: SERPINF1 as ready
BabyScreen+ newborn screening v0.2095 SERPINF1 Zornitza Stark Gene: serpinf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2095 SERPINF1 Zornitza Stark Classified gene: SERPINF1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2095 SERPINF1 Zornitza Stark Gene: serpinf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2094 SERPINF1 Zornitza Stark gene: SERPINF1 was added
gene: SERPINF1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, skeletal tags were added to gene: SERPINF1.
Mode of inheritance for gene: SERPINF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINF1 were set to 28689307
Phenotypes for gene: SERPINF1 were set to Osteogenesis imperfecta, type VI, MIM# 613982
Review for gene: SERPINF1 was set to GREEN
Added comment: Established gene-disease association.

Onset of fractures is in infancy.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
BabyScreen+ newborn screening v0.2093 PPIB Zornitza Stark Marked gene: PPIB as ready
BabyScreen+ newborn screening v0.2093 PPIB Zornitza Stark Gene: ppib has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2093 PPIB Zornitza Stark gene: PPIB was added
gene: PPIB was added to Baby Screen+ newborn screening. Sources: Expert list
skeletal tags were added to gene: PPIB.
Mode of inheritance for gene: PPIB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIB were set to 19781681; 32392875
Phenotypes for gene: PPIB were set to Osteogenesis imperfecta, type IX, MIM# 259440
Review for gene: PPIB was set to RED
Added comment: Established gene-diseases association.

Most reported families have had severe OI, presenting perinatally, therefore exclude.
Sources: Expert list
BabyScreen+ newborn screening v0.2092 PLOD2 Zornitza Stark Marked gene: PLOD2 as ready
BabyScreen+ newborn screening v0.2092 PLOD2 Zornitza Stark Gene: plod2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2092 PLOD2 Zornitza Stark Phenotypes for gene: PLOD2 were changed from Bruck syndrome to Bruck syndrome 2, MIM# 609220
BabyScreen+ newborn screening v0.2091 PLOD2 Zornitza Stark reviewed gene: PLOD2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bruck syndrome 2, MIM# 609220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2091 P3H1 Zornitza Stark Marked gene: P3H1 as ready
BabyScreen+ newborn screening v0.2091 P3H1 Zornitza Stark Gene: p3h1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2091 P3H1 Zornitza Stark Classified gene: P3H1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2091 P3H1 Zornitza Stark Gene: p3h1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2090 P3H1 Zornitza Stark gene: P3H1 was added
gene: P3H1 was added to Baby Screen+ newborn screening. Sources: Expert Review
treatable, skeletal tags were added to gene: P3H1.
Mode of inheritance for gene: P3H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: P3H1 were set to 17277775; 18566967
Phenotypes for gene: P3H1 were set to Osteogenesis imperfecta, type VIII, (MIM# 610915)
Review for gene: P3H1 was set to GREEN
Added comment: More than 15 families reported.

Congenital onset.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert Review
BabyScreen+ newborn screening v0.2089 MESD Zornitza Stark Marked gene: MESD as ready
BabyScreen+ newborn screening v0.2089 MESD Zornitza Stark Gene: mesd has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2089 MESD Zornitza Stark Classified gene: MESD as Green List (high evidence)
BabyScreen+ newborn screening v0.2089 MESD Zornitza Stark Gene: mesd has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2088 MESD Zornitza Stark gene: MESD was added
gene: MESD was added to Baby Screen+ newborn screening. Sources: Expert Review
treatable, skeletal tags were added to gene: MESD.
Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MESD were set to 31564437; 35092157; 33596325; 31564437
Phenotypes for gene: MESD were set to Osteogenesis imperfecta, type XX, MIM# 618644
Review for gene: MESD was set to GREEN
Added comment: More than 5 families reported.

Severe form of OI, some perinatal lethal.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert Review
BabyScreen+ newborn screening v0.2087 KDELR2 Zornitza Stark Marked gene: KDELR2 as ready
BabyScreen+ newborn screening v0.2087 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2087 KDELR2 Zornitza Stark Classified gene: KDELR2 as Green List (high evidence)
BabyScreen+ newborn screening v0.2087 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2086 KDELR2 Zornitza Stark gene: KDELR2 was added
gene: KDELR2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, skeletal tags were added to gene: KDELR2.
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KDELR2 were set to Osteogenesis imperfecta 21, MIM# 619131
Review for gene: KDELR2 was set to GREEN
Added comment: 4 families with osteogenesis imperfecta reported with functional studies.

Onset in infancy.

Improvement reported with bisphosphanates, similar to other OI.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
BabyScreen+ newborn screening v0.2085 FKBP10 Zornitza Stark Marked gene: FKBP10 as ready
BabyScreen+ newborn screening v0.2085 FKBP10 Zornitza Stark Gene: fkbp10 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2085 FKBP10 Zornitza Stark Classified gene: FKBP10 as Green List (high evidence)
BabyScreen+ newborn screening v0.2085 FKBP10 Zornitza Stark Gene: fkbp10 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2084 FKBP10 Zornitza Stark Tag treatable tag was added to gene: FKBP10.
Tag skeletal tag was added to gene: FKBP10.
BabyScreen+ newborn screening v0.2084 FKBP10 Zornitza Stark gene: FKBP10 was added
gene: FKBP10 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: FKBP10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKBP10 were set to 34173012
Phenotypes for gene: FKBP10 were set to Osteogenesis imperfecta, type XI, OMIM:610968
Review for gene: FKBP10 was set to GREEN
Added comment: Well established gene-disease association.

Early-onset bone fractures and progressive skeletal deformities.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
BabyScreen+ newborn screening v0.2083 BMP1 Zornitza Stark Marked gene: BMP1 as ready
BabyScreen+ newborn screening v0.2083 BMP1 Zornitza Stark Gene: bmp1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2083 BMP1 Zornitza Stark Classified gene: BMP1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2083 BMP1 Zornitza Stark Gene: bmp1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2082 BMP1 Zornitza Stark gene: BMP1 was added
gene: BMP1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: BMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BMP1 were set to 33818922
Phenotypes for gene: BMP1 were set to Osteogenesis imperfecta, type XIII , MIM#614856
Review for gene: BMP1 was set to GREEN
Added comment: Rare cause of OI. 20 families reported.

Treatment: bisphosphanates.
Sources: Expert list
BabyScreen+ newborn screening v0.2081 PTH1R Zornitza Stark changed review comment from: Variants in this gene are associated with a range of skeletal disorder.

Wide variability in severity, with BOCD manifesting antenatally.

No specific treatment.; to: Variants in this gene are associated with a range of skeletal disorders.

Wide variability in severity, with BOCD manifesting antenatally.

No specific treatment.
BabyScreen+ newborn screening v0.2081 SARS Zornitza Stark Marked gene: SARS as ready
BabyScreen+ newborn screening v0.2081 SARS Zornitza Stark Gene: sars has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2081 SARS Zornitza Stark Classified gene: SARS as Red List (low evidence)
BabyScreen+ newborn screening v0.2081 SARS Zornitza Stark Gene: sars has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2080 SCARB2 Zornitza Stark Marked gene: SCARB2 as ready
BabyScreen+ newborn screening v0.2080 SCARB2 Zornitza Stark Gene: scarb2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2080 SCARB2 Zornitza Stark Classified gene: SCARB2 as Red List (low evidence)
BabyScreen+ newborn screening v0.2080 SCARB2 Zornitza Stark Gene: scarb2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2079 SERPING1 Zornitza Stark Marked gene: SERPING1 as ready
BabyScreen+ newborn screening v0.2079 SERPING1 Zornitza Stark Gene: serping1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2079 SERPING1 Zornitza Stark Classified gene: SERPING1 as Red List (low evidence)
BabyScreen+ newborn screening v0.2079 SERPING1 Zornitza Stark Gene: serping1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2078 SERPING1 Zornitza Stark Tag treatable tag was added to gene: SERPING1.
Tag immunological tag was added to gene: SERPING1.
BabyScreen+ newborn screening v0.2078 SGPL1 Zornitza Stark Marked gene: SGPL1 as ready
BabyScreen+ newborn screening v0.2078 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2078 SGPL1 Zornitza Stark Classified gene: SGPL1 as Red List (low evidence)
BabyScreen+ newborn screening v0.2078 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2077 SGPL1 Zornitza Stark Tag renal tag was added to gene: SGPL1.
BabyScreen+ newborn screening v0.2077 SLC1A3 Zornitza Stark Marked gene: SLC1A3 as ready
BabyScreen+ newborn screening v0.2077 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2077 SLC1A3 Zornitza Stark Classified gene: SLC1A3 as Red List (low evidence)
BabyScreen+ newborn screening v0.2077 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2076 SLC1A3 Zornitza Stark Tag neurological tag was added to gene: SLC1A3.
BabyScreen+ newborn screening v0.2076 SMARCD2 Zornitza Stark Marked gene: SMARCD2 as ready
BabyScreen+ newborn screening v0.2076 SMARCD2 Zornitza Stark Gene: smarcd2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2076 SMARCD2 Zornitza Stark Classified gene: SMARCD2 as Green List (high evidence)
BabyScreen+ newborn screening v0.2076 SMARCD2 Zornitza Stark Gene: smarcd2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2075 SMARCD2 Zornitza Stark Tag treatable tag was added to gene: SMARCD2.
Tag immunological tag was added to gene: SMARCD2.
BabyScreen+ newborn screening v0.2075 SMARCD2 Zornitza Stark reviewed gene: SMARCD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Specific granule deficiency 2 MIM#617475; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2075 SNX10 Zornitza Stark Marked gene: SNX10 as ready
BabyScreen+ newborn screening v0.2075 SNX10 Zornitza Stark Gene: snx10 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2075 SNX10 Zornitza Stark Classified gene: SNX10 as Green List (high evidence)
BabyScreen+ newborn screening v0.2075 SNX10 Zornitza Stark Gene: snx10 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2074 SNX10 Zornitza Stark Tag treatable tag was added to gene: SNX10.
Tag skeletal tag was added to gene: SNX10.
BabyScreen+ newborn screening v0.2074 SORD Zornitza Stark Marked gene: SORD as ready
BabyScreen+ newborn screening v0.2074 SORD Zornitza Stark Gene: sord has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2074 SORD Zornitza Stark Classified gene: SORD as Red List (low evidence)
BabyScreen+ newborn screening v0.2074 SORD Zornitza Stark Gene: sord has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2073 SORD Zornitza Stark Tag treatable tag was added to gene: SORD.
Tag metabolic tag was added to gene: SORD.
BabyScreen+ newborn screening v0.2073 SOX3 Zornitza Stark Marked gene: SOX3 as ready
BabyScreen+ newborn screening v0.2073 SOX3 Zornitza Stark Gene: sox3 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2073 SOX3 Zornitza Stark Classified gene: SOX3 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2073 SOX3 Zornitza Stark Gene: sox3 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2072 SOX3 Zornitza Stark Tag for review tag was added to gene: SOX3.
Tag treatable tag was added to gene: SOX3.
Tag endocrine tag was added to gene: SOX3.
BabyScreen+ newborn screening v0.2072 SOX3 Zornitza Stark reviewed gene: SOX3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Panhypopituitarism, X-linked MIM#312000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.2072 STAT1 Zornitza Stark Marked gene: STAT1 as ready
BabyScreen+ newborn screening v0.2072 STAT1 Zornitza Stark Gene: stat1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2072 STAT1 Zornitza Stark Mode of inheritance for gene: STAT1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2071 STAT1 Zornitza Stark Classified gene: STAT1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2071 STAT1 Zornitza Stark Gene: stat1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2070 STAT1 Zornitza Stark Tag treatable tag was added to gene: STAT1.
Tag immunological tag was added to gene: STAT1.
BabyScreen+ newborn screening v0.2070 STAT1 Zornitza Stark reviewed gene: STAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive, MIM# 613796; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2070 STIM1 Zornitza Stark Marked gene: STIM1 as ready
BabyScreen+ newborn screening v0.2070 STIM1 Zornitza Stark Gene: stim1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2070 STIM1 Zornitza Stark Classified gene: STIM1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2070 STIM1 Zornitza Stark Gene: stim1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2069 STIM1 Zornitza Stark Tag treatable tag was added to gene: STIM1.
Tag immunological tag was added to gene: STIM1.
BabyScreen+ newborn screening v0.2069 STIM1 Zornitza Stark reviewed gene: STIM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 10 MIM612783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2069 STK4 Zornitza Stark Marked gene: STK4 as ready
BabyScreen+ newborn screening v0.2069 STK4 Zornitza Stark Gene: stk4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2069 STK4 Zornitza Stark Classified gene: STK4 as Green List (high evidence)
BabyScreen+ newborn screening v0.2069 STK4 Zornitza Stark Gene: stk4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2068 STK4 Zornitza Stark Tag treatable tag was added to gene: STK4.
Tag immunological tag was added to gene: STK4.
BabyScreen+ newborn screening v0.2068 STK4 Zornitza Stark reviewed gene: STK4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations MIM#614868; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2068 STX16 Zornitza Stark Marked gene: STX16 as ready
BabyScreen+ newborn screening v0.2068 STX16 Zornitza Stark Gene: stx16 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2068 STX16 Zornitza Stark Classified gene: STX16 as Green List (high evidence)
BabyScreen+ newborn screening v0.2068 STX16 Zornitza Stark Gene: stx16 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2067 STX16 Zornitza Stark Tag treatable tag was added to gene: STX16.
Tag endocrine tag was added to gene: STX16.
BabyScreen+ newborn screening v0.2067 SYT2 Zornitza Stark Marked gene: SYT2 as ready
BabyScreen+ newborn screening v0.2067 SYT2 Zornitza Stark Gene: syt2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2067 SYT2 Zornitza Stark Mode of inheritance for gene: SYT2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2066 SYT2 Zornitza Stark Classified gene: SYT2 as Green List (high evidence)
BabyScreen+ newborn screening v0.2066 SYT2 Zornitza Stark Gene: syt2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2065 SYT2 Zornitza Stark Tag treatable tag was added to gene: SYT2.
Tag neurological tag was added to gene: SYT2.
BabyScreen+ newborn screening v0.2065 TBL1X Zornitza Stark Marked gene: TBL1X as ready
BabyScreen+ newborn screening v0.2065 TBL1X Zornitza Stark Gene: tbl1x has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2065 TBL1X Zornitza Stark Classified gene: TBL1X as Green List (high evidence)
BabyScreen+ newborn screening v0.2065 TBL1X Zornitza Stark Gene: tbl1x has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2064 TBL1X Zornitza Stark Tag treatable tag was added to gene: TBL1X.
Tag endocrine tag was added to gene: TBL1X.
BabyScreen+ newborn screening v0.2064 TF Zornitza Stark Marked gene: TF as ready
BabyScreen+ newborn screening v0.2064 TF Zornitza Stark Gene: tf has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2064 TF Zornitza Stark Classified gene: TF as Green List (high evidence)
BabyScreen+ newborn screening v0.2064 TF Zornitza Stark Gene: tf has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2063 TF Zornitza Stark Tag treatable tag was added to gene: TF.
Tag haematological tag was added to gene: TF.
BabyScreen+ newborn screening v0.2063 SARS Lilian Downie gene: SARS was added
gene: SARS was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS were set to PMID:34570399, PMID: 34194004
Phenotypes for gene: SARS were set to Neurodevelopmental disorder with microcephaly, ataxia, and seizures MIM#617709
Review for gene: SARS was set to RED
Added comment: developmental delay, deafness, cardiomyopathy, epilepsy, and severe febrile decompensations
Rx serine supplementation - limited evidence and sounds supportive only
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SCARB2 Lilian Downie gene: SCARB2 was added
gene: SCARB2 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SCARB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCARB2 were set to PMID: 34337151, PMID: 35346091, PMID: 26677510
Phenotypes for gene: SCARB2 were set to Epilepsy, progressive myoclonic 4, with or without renal failure MIM#254900
Review for gene: SCARB2 was set to RED
Added comment: Onset not <5
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SERPING1 Lilian Downie gene: SERPING1 was added
gene: SERPING1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SERPING1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SERPING1 were set to PMID: 32898710
Phenotypes for gene: SERPING1 were set to Angioedema, hereditary, 1 and 2 MIM#106100
Review for gene: SERPING1 was set to RED
Added comment: episodic local subcutaneous edema and submucosal edema involving the upper respiratory and gastrointestinal tracts.

Age of onset not typically <5

Treatment Purified C1 inhibitor concentrate (Cinryze, Berinert, HAEGARDA, or Ruconest), Ecallantide (Kalbitor), Icatibant (Firazyr), Lanadelumab, Orladeyo (berotralstat), FFP or solvent-detergent treated plasma, antisense oligonucleotide treatment (donidalorsen)
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SGPL1 Lilian Downie gene: SGPL1 was added
gene: SGPL1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SGPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGPL1 were set to PMID: 28165343
Phenotypes for gene: SGPL1 were set to Nephrotic syndrome, type 14 MIM#617575
Review for gene: SGPL1 was set to RED
Added comment: infancy or early childhood with progressive renal dysfunction associated with focal segmental glomerulosclerosis (FSGS), resulting in end-stage renal disease within a few years. Other infants present with primary adrenal insufficiency. Some patients present in utero with fetal hydrops and fetal demise. Additional features of the disorder can include ichthyosis, acanthosis, adrenal insufficiency, immunodeficiency, and neurologic defects

Rx Hydrocortisone, kidney transplant (treatment doesn't fit screening model as would need to have ESRD before you had it?)
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SLC1A3 Lilian Downie gene: SLC1A3 was added
gene: SLC1A3 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SLC1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A3 were set to PMID: 32754645
Phenotypes for gene: SLC1A3 were set to Episodic ataxia, type 6 MIM#612656
Review for gene: SLC1A3 was set to RED
Added comment: ataxia occurs with febrile illnesses
Episodic attacks lasted 2 to 3 hours and were often associated with nausea, vomiting, photophobia, phonophobia, vertigo, diplopia, and/or slurred speech
Not consistently in children <5 and variable severity

Suggested Rx acetazolamide
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SMARCD2 Lilian Downie gene: SMARCD2 was added
gene: SMARCD2 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SMARCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMARCD2 were set to PubMed: 28369036, 33279574, 33025377
Phenotypes for gene: SMARCD2 were set to Specific granule deficiency 2 MIM#617475
Review for gene: SMARCD2 was set to GREEN
Added comment: recurrent infections due to defective neutrophil development. Bone marrow findings include paucity of neutrophil granulocytes, absence of granule proteins in neutrophils, abnormal megakaryocytes, and features of progressive myelofibrosis with blasts. The disorder is apparent from infancy, and patients may die in early childhood unless they undergo hematopoietic stem cell transplantation. Most patients have additional findings, including delayed development, mild dysmorphic features, tooth abnormalities, and distal skeletal defects

Rx bone marrow transplant
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SNX10 Lilian Downie gene: SNX10 was added
gene: SNX10 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SNX10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNX10 were set to PMID: 30885997, PMID: 22499339
Phenotypes for gene: SNX10 were set to Osteopetrosis, autosomal recessive 8 MIM#615085
Review for gene: SNX10 was set to GREEN
Added comment: macrocephaly
failure to thrive
osteopetrosis

Rx bone marrow tranplant
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SORD Lilian Downie gene: SORD was added
gene: SORD was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SORD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SORD were set to PMID: 32367058
Phenotypes for gene: SORD were set to Sorbitol dehydrogenase deficiency with peripheral neuropathy MIM#618912
Review for gene: SORD was set to RED
Added comment: Slowly progressive, onset not consistently <5

Rx epalrestat and ranirestat
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SOX3 Lilian Downie gene: SOX3 was added
gene: SOX3 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SOX3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SOX3 were set to PMID: 31678974, PMID: 15800844
Phenotypes for gene: SOX3 were set to Panhypopituitarism, X-linked MIM#312000
Review for gene: SOX3 was set to AMBER
Added comment: Amber in our mendeliome - reviewed for ID
Green in pituitary disorders

Xq27.1 duplication most common mechanism - inclusion might be a question of whether we can detect CNV's in this region

neonatal hypoglycemia and growth hormone deficiency in addition to variable deficiencies of other pituitary hormones. Brain hypoplasia of the anterior pituitary with hypoplasia or absence of the lower half of the infundibulum

Rx Growth hormone, levothyroxine, hydrocortisone
Sources: Expert list
BabyScreen+ newborn screening v0.2063 STAT1 Lilian Downie gene: STAT1 was added
gene: STAT1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: STAT1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: STAT1 were set to PMID: 31512162, PMID: 27117246
Phenotypes for gene: STAT1 were set to Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive MIM#613796
Review for gene: STAT1 was set to GREEN
Added comment: combined immunodeficiency
autosomal recessive (AR) complete STAT1 deficiency, AR partial STAT1 deficiency, autosomal dominant (AD) STAT1 deficiency, and AD STAT1 gain-of-function.
gain of function mutations - treat rituxomab
complete - treat BMT
Sources: Expert list
BabyScreen+ newborn screening v0.2063 STIM1 Lilian Downie gene: STIM1 was added
gene: STIM1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: STIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STIM1 were set to PMID: 26469693, PMID: 30949876, PMID: 26560041
Phenotypes for gene: STIM1 were set to Immunodeficiency 10 MIM612783
Review for gene: STIM1 was set to GREEN
Added comment: recurrent infections in childhood due to defective T- and NK-cell function, although the severity is variable. Affected individuals may also have hypotonia, hypohidrosis, or dental enamel hypoplasia consistent with amelogenesis imperfecta

Rx bone marrow transpant

Age of onset is consistently <5 but the severity of infections is highly variable - treatment if the phenotype is severe
Sources: Expert list
BabyScreen+ newborn screening v0.2063 STK4 Lilian Downie gene: STK4 was added
gene: STK4 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: STK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STK4 were set to PMID: 22294732
Phenotypes for gene: STK4 were set to T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations MIM#614868
Review for gene: STK4 was set to GREEN
Added comment: primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, autoimmune manifestations, and cardiac malformations, including atrial septal defect

Rx bone marrow transplant
Sources: Expert list
BabyScreen+ newborn screening v0.2063 STX16 Lilian Downie gene: STX16 was added
gene: STX16 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: STX16 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: STX16 were set to PMID: 33247854, PMID: 34477200, PMID: 29072892
Phenotypes for gene: STX16 were set to Pseudohypoparathyroidism, type IB MIM#603233
Review for gene: STX16 was set to GREEN
Added comment: characterized clinically by isolated renal PTH resistance manifest as hypocalcemia, hyperphosphatemia, and increased serum PTH
without other features of Albright hereditary osteodystrophy
Rx Calcium, calcitriol, levothyroxine, growth hormone
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SYT2 Lilian Downie gene: SYT2 was added
gene: SYT2 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SYT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SYT2 were set to PMID: 32250532, 32776697
Phenotypes for gene: SYT2 were set to Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461
Review for gene: SYT2 was set to GREEN
Added comment: Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.

Only report biallelic for newborn screening ?
monoallelic causes a later onset distal weakness/neuropathy phenotype - still childhood but variable or not clear - not consistently <5yrs
Sources: Expert list
BabyScreen+ newborn screening v0.2063 TBL1X Lilian Downie gene: TBL1X was added
gene: TBL1X was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TBL1X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: TBL1X were set to PMID: 27603907
Phenotypes for gene: TBL1X were set to Hypothyroidism, congenital, nongoitrous, 8 MIM#301033
Review for gene: TBL1X was set to GREEN
Added comment: Small thyroid gland
Detected on newborn screening
Can affect carrier females but more mildly
Association with deafness

Rx thyroxine
Sources: Expert list
BabyScreen+ newborn screening v0.2063 TF Lilian Downie gene: TF was added
gene: TF was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TF were set to PMID: 32028041, PMID: 19579082, PMID: 11110675
Phenotypes for gene: TF were set to Atransferrinemia MIM#209300
Review for gene: TF was set to GREEN
Added comment: Hypochromic microcytic anaemia from absent transferrin - presents in infancy


Rx Red cell transfusions, deferoxamine
Sources: Expert list
BabyScreen+ newborn screening v0.2063 SAR1B Zornitza Stark Marked gene: SAR1B as ready
BabyScreen+ newborn screening v0.2063 SAR1B Zornitza Stark Gene: sar1b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2063 SAR1B Zornitza Stark Classified gene: SAR1B as Green List (high evidence)
BabyScreen+ newborn screening v0.2063 SAR1B Zornitza Stark Gene: sar1b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2062 SAR1B Zornitza Stark gene: SAR1B was added
gene: SAR1B was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, gastrointestinal tags were added to gene: SAR1B.
Mode of inheritance for gene: SAR1B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SAR1B were set to Chylomicron retention disease, MIM# 246700
Review for gene: SAR1B was set to GREEN
Added comment: Chylomicron retention disease is an autosomal recessive disorder of severe fat malabsorption associated with failure to thrive in infancy. Well established gene-disease association.

Congenital onset.

Treatment: low-fat diet with supplementation of fat-soluble vitamins (A, D, E, and K) and oral essential fatty acid supplementation

Non-genetic confirmatory testing: total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol
Sources: Expert list
BabyScreen+ newborn screening v0.2061 SAMD9L Zornitza Stark Marked gene: SAMD9L as ready
BabyScreen+ newborn screening v0.2061 SAMD9L Zornitza Stark Gene: samd9l has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2061 SAMD9L Zornitza Stark Classified gene: SAMD9L as Green List (high evidence)
BabyScreen+ newborn screening v0.2061 SAMD9L Zornitza Stark Gene: samd9l has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2060 SAMD9L Zornitza Stark gene: SAMD9L was added
gene: SAMD9L was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological, haematological tags were added to gene: SAMD9L.
Mode of inheritance for gene: SAMD9L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SAMD9L were set to 31306780
Phenotypes for gene: SAMD9L were set to Ataxia-pancytopenia syndrome, MIM# 159550
Review for gene: SAMD9L was set to GREEN
Added comment: At least three unrelated families reported, some postulate GoF whereas others postulate LoF as mechanism.

Ataxia-pancytopenia syndrome (ATXPC) is an autosomal dominant disorder characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to bone marrow failure and myeloid leukemia. The germline genetic defect is associated with somatic loss of chromosome 7 (monosomy 7) resulting in the deletion of several genes on chromosome 7 that may predispose to the development of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML).

Treatment: BMT.

Non-genetic confirmatory testing: no.
Sources: Expert list
BabyScreen+ newborn screening v0.2059 SAMD9 Zornitza Stark Marked gene: SAMD9 as ready
BabyScreen+ newborn screening v0.2059 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2059 SAMD9 Zornitza Stark Classified gene: SAMD9 as Green List (high evidence)
BabyScreen+ newborn screening v0.2059 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2058 SAMD9 Zornitza Stark gene: SAMD9 was added
gene: SAMD9 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SAMD9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SAMD9 were set to 31306780
Phenotypes for gene: SAMD9 were set to MIRAGE syndrome, MIM# 617053
Review for gene: SAMD9 was set to GREEN
Added comment: MIRAGE syndrome (MIRAGE) is a form of syndromic adrenal hypoplasia, characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. The condition is often fatal within the first decade of life, usually as a result of invasive infection.

Treatment: BMT.

Non-genetic confirmatory testing: no.
Sources: Expert list
BabyScreen+ newborn screening v0.2057 THAP11 Zornitza Stark Marked gene: THAP11 as ready
BabyScreen+ newborn screening v0.2057 THAP11 Zornitza Stark Gene: thap11 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2057 THAP11 Zornitza Stark Phenotypes for gene: THAP11 were changed from Combined methylmalonic acidemia and homocystinuria, cblX like 2 to Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related
BabyScreen+ newborn screening v0.2056 THAP11 Zornitza Stark Classified gene: THAP11 as Red List (low evidence)
BabyScreen+ newborn screening v0.2056 THAP11 Zornitza Stark Gene: thap11 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2055 TMEM165 Zornitza Stark Marked gene: TMEM165 as ready
BabyScreen+ newborn screening v0.2055 TMEM165 Zornitza Stark Gene: tmem165 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2055 TMEM165 Zornitza Stark Classified gene: TMEM165 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2055 TMEM165 Zornitza Stark Gene: tmem165 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2054 TMEM165 Zornitza Stark Tag metabolic tag was added to gene: TMEM165.
BabyScreen+ newborn screening v0.2054 TMEM165 Zornitza Stark reviewed gene: TMEM165: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IIk MIM#614727; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.2054 TNFRSF13B Zornitza Stark Marked gene: TNFRSF13B as ready
BabyScreen+ newborn screening v0.2054 TNFRSF13B Zornitza Stark Gene: tnfrsf13b has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2054 TNFRSF13B Zornitza Stark Classified gene: TNFRSF13B as Red List (low evidence)
BabyScreen+ newborn screening v0.2054 TNFRSF13B Zornitza Stark Gene: tnfrsf13b has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2053 TNFRSF13B Zornitza Stark Tag treatable tag was added to gene: TNFRSF13B.
Tag immunological tag was added to gene: TNFRSF13B.
BabyScreen+ newborn screening v0.2053 TNFAIP3 Zornitza Stark Marked gene: TNFAIP3 as ready
BabyScreen+ newborn screening v0.2053 TNFAIP3 Zornitza Stark Gene: tnfaip3 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2053 TNFAIP3 Zornitza Stark Classified gene: TNFAIP3 as Red List (low evidence)
BabyScreen+ newborn screening v0.2053 TNFAIP3 Zornitza Stark Gene: tnfaip3 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2052 TNFAIP3 Zornitza Stark Tag treatable tag was added to gene: TNFAIP3.
Tag immunological tag was added to gene: TNFAIP3.
BabyScreen+ newborn screening v0.2052 THAP11 Lilian Downie gene: THAP11 was added
gene: THAP11 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: THAP11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THAP11 were set to PMID: 28449119, PMID: 31905202
Phenotypes for gene: THAP11 were set to Combined methylmalonic acidemia and homocystinuria, cblX like 2
Review for gene: THAP11 was set to RED
Added comment: Single patient?
Not in our mendeliome
Not enough gene disease validity
Sources: Expert list
BabyScreen+ newborn screening v0.2052 TMEM165 Lilian Downie gene: TMEM165 was added
gene: TMEM165 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TMEM165 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM165 were set to PMID: 28323990, PMID: 35693943, PMID: 22683087
Phenotypes for gene: TMEM165 were set to Congenital disorder of glycosylation, type IIk MIM#614727
Review for gene: TMEM165 was set to AMBER
Added comment: Affected individuals show psychomotor retardation and growth retardation, and most have short stature. Other features include dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia. Serum transferrin analysis shows a CDG type II pattern

Rx D-galactose (single paper, 2 unrelated patients and an in vitro study) ?inadequete evidence for treatment? Might need to check with JC if we would offer it maybe include
Sources: Expert list
BabyScreen+ newborn screening v0.2052 TNFRSF13B Lilian Downie gene: TNFRSF13B was added
gene: TNFRSF13B was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TNFRSF13B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TNFRSF13B were set to PMID: 31681716, PMID: 18981294
Phenotypes for gene: TNFRSF13B were set to Immunodeficiency, common variable, 2 MIM#240500
Review for gene: TNFRSF13B was set to RED
Added comment: hypogammaglobulinemia with low serum IgG, IgM, and IgA, and recurrent infections, including otitis media, respiratory tract infections, and gastrointestinal tract infections. Serum IgG and IgA were low, and serum antibody response to immunization with pneumococcal vaccine was decreased, although T cell-dependent response to tetanus toxin was normal.

I think the age of onset is too variable .

Rx immunoglobulin
Sources: Expert list
BabyScreen+ newborn screening v0.2052 TNFAIP3 Lilian Downie gene: TNFAIP3 was added
gene: TNFAIP3 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TNFAIP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNFAIP3 were set to PMID: 31587140, PMID: 33101300
Phenotypes for gene: TNFAIP3 were set to Autoinflammatory syndrome, familial, Behcet-like 1 MIM#616744
Review for gene: TNFAIP3 was set to RED
Added comment: Average age of onset 5yrs - too variable re age of onset.

painful and recurrent mucosal ulceration affecting the oral mucosa, gastrointestinal tract, and genital areas. The onset of symptoms is usually in the first decade, although later onset has been reported. Additional more variable features include skin rash, uveitis, and polyarthritis, consistent with a systemic hyperinflammatory state. Many patients have evidence of autoimmune disease. Rare patients may also have concurrent features of immunodeficiency, including recurrent infections with low numbers of certain white blood cells or impaired function of immune cells.

Treatment: Colchicine, glucocorticoid, mesalazine, cyclosporine, methotrexate, azathioprine, anakinra, rituximab, tocilizumab, infliximab
Sources: Expert list
BabyScreen+ newborn screening v0.2052 RNPC3 Zornitza Stark Marked gene: RNPC3 as ready
BabyScreen+ newborn screening v0.2052 RNPC3 Zornitza Stark Gene: rnpc3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2052 RNPC3 Zornitza Stark Classified gene: RNPC3 as Green List (high evidence)
BabyScreen+ newborn screening v0.2052 RNPC3 Zornitza Stark Gene: rnpc3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2051 RNPC3 Zornitza Stark gene: RNPC3 was added
gene: RNPC3 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: RNPC3.
Mode of inheritance for gene: RNPC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNPC3 were set to 29866761; 32462814; 33650182
Phenotypes for gene: RNPC3 were set to Pituitary hormone deficiency, combined or isolated, 7, MIM# 618160
Review for gene: RNPC3 was set to GREEN
Added comment: Three unrelated individuals reported with combined and isolated pituitary hormone deficiencies, including GH and TSH.

Onset: congenital.

Treatment: GH, thyroxine.

Non-genetic confirmatory testing: hormone levels.
Sources: Expert list
BabyScreen+ newborn screening v0.2050 RASGRP1 Zornitza Stark Marked gene: RASGRP1 as ready
BabyScreen+ newborn screening v0.2050 RASGRP1 Zornitza Stark Gene: rasgrp1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2050 RASGRP1 Zornitza Stark Classified gene: RASGRP1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2050 RASGRP1 Zornitza Stark Gene: rasgrp1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2049 RASGRP1 Zornitza Stark gene: RASGRP1 was added
gene: RASGRP1 was added to Baby Screen+ newborn screening. Sources: Literature
treatable, immunological tags were added to gene: RASGRP1.
Mode of inheritance for gene: RASGRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RASGRP1 were set to Immunodeficiency 64 (MIM#618534)
Review for gene: RASGRP1 was set to GREEN
Added comment: Immunodeficiency-64 with lymphoproliferation (IMD64) is an autosomal recessive primary immunodeficiency characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Laboratory studies show variably decreased numbers of T cells, with lesser deficiencies of B and NK cells. There is impaired T-cell proliferation and activation; functional defects in B cells and NK cells may also be observed. Patients have increased susceptibility to EBV infection and may develop lymphoproliferation or EBV-associated lymphoma. Some patients may develop features of autoimmunity.

Severe disorder, fatal outcomes reported in childhood.

Treatment: BMT.

Non-genetic confirmatory testing: no.
Sources: Literature
BabyScreen+ newborn screening v0.2048 RAC2 Zornitza Stark Marked gene: RAC2 as ready
BabyScreen+ newborn screening v0.2048 RAC2 Zornitza Stark Gene: rac2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2048 RAC2 Zornitza Stark Phenotypes for gene: RAC2 were changed from Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia MIM# 618986 to Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopenia MIM# 618986
BabyScreen+ newborn screening v0.2047 RAC2 Zornitza Stark Classified gene: RAC2 as Green List (high evidence)
BabyScreen+ newborn screening v0.2047 RAC2 Zornitza Stark Gene: rac2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2046 RAC2 Zornitza Stark gene: RAC2 was added
gene: RAC2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: RAC2.
Mode of inheritance for gene: RAC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAC2 were set to Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia MIM# 618986
Review for gene: RAC2 was set to GREEN
Added comment: Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia
13 individuals from 8 unrelated families; mono-allelic; gain of function; multiple mouse models

Mono-allelic missense variants were reported in each individual (5 x De Novo) and resulted in a gain-of -function. (E62K, P34H, N92T, G12R)

These individuals typically presented in infancy with frequent infections, profound leukopaenia, lymphopaenia diarrhoea and hypogammaglobulinaemia.

SCID-like phenotype.

Treatment: IVIG, BMT

Note evidence for the other two immunodeficiency disorders associated with this gene is limited.
Sources: Expert list
BabyScreen+ newborn screening v0.2045 PLS3 Zornitza Stark Marked gene: PLS3 as ready
BabyScreen+ newborn screening v0.2045 PLS3 Zornitza Stark Gene: pls3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2045 PLS3 Zornitza Stark Classified gene: PLS3 as Green List (high evidence)
BabyScreen+ newborn screening v0.2045 PLS3 Zornitza Stark Gene: pls3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2044 PLS3 Zornitza Stark Tag treatable tag was added to gene: PLS3.
Tag skeletal tag was added to gene: PLS3.
BabyScreen+ newborn screening v0.2044 PLS3 Zornitza Stark gene: PLS3 was added
gene: PLS3 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: PLS3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLS3 were set to 32655496; 25209159; 29736964; 29884797; 28777485; 24088043
Phenotypes for gene: PLS3 were set to Bone mineral density QTL18, osteoporosis - MIM#300910
Review for gene: PLS3 was set to GREEN
Added comment: Females mildly affected: exclude from screening.

Presentation in males similar to OI, though also variable in severity.

Treatment: safe handling techniques, bisphosphonates, pamidronate, zoledronic acid, teriparatide, denosumab, alendronate

Non-genetic confirmatory testing: skeletal survey
Sources: Expert list
BabyScreen+ newborn screening v0.2043 OTULIN Zornitza Stark Marked gene: OTULIN as ready
BabyScreen+ newborn screening v0.2043 OTULIN Zornitza Stark Gene: otulin has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2043 OTULIN Zornitza Stark Classified gene: OTULIN as Green List (high evidence)
BabyScreen+ newborn screening v0.2043 OTULIN Zornitza Stark Gene: otulin has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2042 OTULIN Zornitza Stark gene: OTULIN was added
gene: OTULIN was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: OTULIN.
Mode of inheritance for gene: OTULIN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OTULIN were set to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099
Review for gene: OTULIN was set to GREEN
Added comment: Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) is an autosomal recessive autoinflammatory disease characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy. Additional features may include diarrhea, increased serum C-reactive protein (CRP), leukocytosis, and neutrophilia in the absence of any infection.

Onset is generally in infancy.

Treatment: inflixiimab, anakinra, etanercept, corticosteroids.

Non-genetic confirmatory testing: no.
Sources: Expert list
BabyScreen+ newborn screening v0.2041 OAS1 Zornitza Stark Marked gene: OAS1 as ready
BabyScreen+ newborn screening v0.2041 OAS1 Zornitza Stark Gene: oas1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2041 OAS1 Zornitza Stark Classified gene: OAS1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2041 OAS1 Zornitza Stark Gene: oas1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2040 OAS1 Zornitza Stark gene: OAS1 was added
gene: OAS1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: OAS1.
Mode of inheritance for gene: OAS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OAS1 were set to 34145065; 29455859
Phenotypes for gene: OAS1 were set to Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinaemia, MIM#618042
Review for gene: OAS1 was set to GREEN
Added comment: Immunodeficiency-100 with pulmonary alveolar proteinosis and hypogammaglobulinemia (IMD100) is primarily a lung disorder characterized by onset of respiratory insufficiency due to pulmonary alveolar proteinosis (PAP) in the first months of life. Affected individuals may have normal respiratory function at birth. Development of the disorder appears to be influenced or triggered by viral infection, manifest as progressive respiratory insufficiency, confluent consolidations on lung imaging, and diffuse collection of periodic acid-Schiff (PAS)-positive material in pulmonary alveoli associated with small and nonfoamy alveolar macrophages. Patients also have hypogammaglobulinemia, leukocytosis, and splenomegaly. Many patients die of respiratory failure in infancy or early childhood.

Treatment: IVIG; BMT is curative.

Non-genetic confirmatory testing: immunoglobulin levels.
Sources: Expert list
BabyScreen+ newborn screening v0.2039 NFKBIA Zornitza Stark Marked gene: NFKBIA as ready
BabyScreen+ newborn screening v0.2039 NFKBIA Zornitza Stark Gene: nfkbia has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2039 NFKBIA Zornitza Stark Classified gene: NFKBIA as Green List (high evidence)
BabyScreen+ newborn screening v0.2039 NFKBIA Zornitza Stark Gene: nfkbia has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2038 NFKBIA Zornitza Stark gene: NFKBIA was added
gene: NFKBIA was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: NFKBIA.
Mode of inheritance for gene: NFKBIA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NFKBIA were set to Ectodermal dysplasia and immunodeficiency 2 MIM# 612132
Review for gene: NFKBIA was set to GREEN
Added comment: 12 heterozygous variants were identified in 15 unrelated individuals (de novo in 14 individuals and somatic mosaicism in 1 individual).

Functional studies & two mouse models; demonstrate reported NFKBIA gain-of-function variants resulting in impaired NFKB1 activity.

The majority of individuals displayed recurrent infections, chronic diarrhoea, agammaglobulinaemia, increased IgM, and defects in teeth (hair, nail, sweat glands).

Onset is generally in infancy.

Treatment: BMT.

Non-genetic confirmatory testing: no
Sources: Expert list
BabyScreen+ newborn screening v0.2037 NAXE Zornitza Stark Marked gene: NAXE as ready
BabyScreen+ newborn screening v0.2037 NAXE Zornitza Stark Gene: naxe has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2037 NAXE Zornitza Stark gene: NAXE was added
gene: NAXE was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: NAXE.
Mode of inheritance for gene: NAXE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXE were set to 27122014; 27616477; 31758406
Phenotypes for gene: NAXE were set to Encephalopathy, progressive, early-onset, with brain oedema and/or leukoencephalopathy, MIM# 617186
Review for gene: NAXE was set to RED
Added comment: Early-onset progressive encephalopathy with brain oedema and/or leukoencephalopathy-1 (PEBEL1) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures, resulting in coma and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions. More than 5 unrelated families reported.

Treatment: niacin

However, single case reported. Treatment not established.
Sources: Expert list
BabyScreen+ newborn screening v0.2036 NAXD Zornitza Stark Marked gene: NAXD as ready
BabyScreen+ newborn screening v0.2036 NAXD Zornitza Stark Gene: naxd has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2036 NAXD Zornitza Stark Classified gene: NAXD as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.2036 NAXD Zornitza Stark Gene: naxd has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.2035 NAXD Zornitza Stark gene: NAXD was added
gene: NAXD was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: NAXD.
Mode of inheritance for gene: NAXD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXD were set to 30576410; 31755961; 32462209; 35231119
Phenotypes for gene: NAXD were set to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 MIM#618321
Review for gene: NAXD was set to AMBER
Added comment: Seven unrelated cases, episodes of fever/infection prior to deterioration reported. Variable phenotype: one patient reported with neurodevelopmental disorder, autism spectrum disorder and a muscular-dystrophy-like myopathy; another with progressive encephalopathy with brain oedema. Patient cells and muscle biopsies also showed impaired mitochondrial function, higher sensitivity to metabolic stress, and decreased mitochondrial reactive oxygen species production. In vitro functional assays also conducted.

Treatment: niacin

However, only two cases reported. Treatment not established.
Sources: Expert list
BabyScreen+ newborn screening v0.2034 MYD88 Zornitza Stark Marked gene: MYD88 as ready
BabyScreen+ newborn screening v0.2034 MYD88 Zornitza Stark Gene: myd88 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2034 MYD88 Zornitza Stark Classified gene: MYD88 as Green List (high evidence)
BabyScreen+ newborn screening v0.2034 MYD88 Zornitza Stark Gene: myd88 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2033 MYD88 Zornitza Stark gene: MYD88 was added
gene: MYD88 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: MYD88.
Mode of inheritance for gene: MYD88 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYD88 were set to 18669862; 20538326; 31301515
Phenotypes for gene: MYD88 were set to Immunodeficiency 68, MIM# 612260
Review for gene: MYD88 was set to GREEN
Added comment: Immunodeficiency-68 (IMD68) is an autosomal recessive primary immunodeficiency characterized by severe systemic and invasive bacterial infections beginning in infancy or early childhood. The most common organisms implicated are Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas, although other organisms may be observed.

At least 7 families and a mouse model.

Treatment: Prophylactic antibiotic treatment, pneumococcal, meningococcal, haemophilus influenzae vaccines, and immunoglobulin replacement.

Non-genetic confirmatory testing: toll-like receptor function
Sources: Expert list
BabyScreen+ newborn screening v0.2032 MTHFS Zornitza Stark Marked gene: MTHFS as ready
BabyScreen+ newborn screening v0.2032 MTHFS Zornitza Stark Gene: mthfs has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2032 MTHFS Zornitza Stark gene: MTHFS was added
gene: MTHFS was added to Baby Screen+ newborn screening. Sources: Expert list
metabolic tags were added to gene: MTHFS.
Mode of inheritance for gene: MTHFS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFS were set to 30031689; 31844630; 22303332
Phenotypes for gene: MTHFS were set to Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, 618367
Review for gene: MTHFS was set to RED
Added comment: Established gene-disease association.

Onset in infancy. Severe disorder.

Treatment: single report of some improvement with combination of oral L-5- methyltetrahydrofolate and intramuscular methylcobalamin
Sources: Expert list
BabyScreen+ newborn screening v0.2031 MTHFD1 Zornitza Stark Marked gene: MTHFD1 as ready
BabyScreen+ newborn screening v0.2031 MTHFD1 Zornitza Stark Gene: mthfd1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2031 MTHFD1 Zornitza Stark Classified gene: MTHFD1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2031 MTHFD1 Zornitza Stark Gene: mthfd1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2030 MTHFD1 Zornitza Stark gene: MTHFD1 was added
gene: MTHFD1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological, haematological tags were added to gene: MTHFD1.
Mode of inheritance for gene: MTHFD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFD1 were set to 32414565; 19033438
Phenotypes for gene: MTHFD1 were set to Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinaemia MIM # 617780
Review for gene: MTHFD1 was set to GREEN
Added comment: 8 individuals from 4 unrelated families have been reported; multiple mouse models

7 individuals were Compound heterozygous (nonsense & missense) and 1 was homozygous (missense) for MTHFD1 variants often resulting in alteration of highly conserved residues in binding-sites.

Individuals typically present with megaloblastic anaemia, atypical hemolytic uremic syndrome, hyperhomocysteinaemia, microangiopathy, recurrent infections and autoimmune diseases.

Treatment: hydroxocobalamin, folinic acid and betaine

Non-genetic confirmatory testing: T and B Lymphocyte and Natural Killer Cell Profile, complete blood count with MCV, plasma homocysteine and methylmalonic acid levels, CSF
Sources: Expert list
BabyScreen+ newborn screening v0.2029 MNX1 Zornitza Stark Marked gene: MNX1 as ready
BabyScreen+ newborn screening v0.2029 MNX1 Zornitza Stark Gene: mnx1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2029 MNX1 Zornitza Stark Classified gene: MNX1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2029 MNX1 Zornitza Stark Gene: mnx1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2028 MNX1 Zornitza Stark gene: MNX1 was added
gene: MNX1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: MNX1.
Mode of inheritance for gene: MNX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MNX1 were set to 36586106
Phenotypes for gene: MNX1 were set to Permanent neonatal diabetes mellitus, MONDO:0100164, MNX1-related
Review for gene: MNX1 was set to GREEN
Added comment: Three unrelated families reported. Presentation is in newborn period.

Treatment: insulin.

Non-genetic confirmatory testing: glucose tolerance test, hemoglobin A1C, insulin level, glucose level
Sources: Expert list
BabyScreen+ newborn screening v0.2027 MALT1 Zornitza Stark Marked gene: MALT1 as ready
BabyScreen+ newborn screening v0.2027 MALT1 Zornitza Stark Gene: malt1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2027 MALT1 Zornitza Stark Classified gene: MALT1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2027 MALT1 Zornitza Stark Gene: malt1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2026 MALT1 Zornitza Stark gene: MALT1 was added
gene: MALT1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: MALT1.
Mode of inheritance for gene: MALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MALT1 were set to Immunodeficiency 12 MIM# 615468
Review for gene: MALT1 was set to GREEN
Added comment: 5 individuals from 3 unrelated families with immunodeficiency phenotype have reported variants in MALT1; two MALT1-knockout mouse models displaying primary T- and B-cell lymphocyte deficiency.

Variants identified were homozygous missense variants resulting in the alteration of highly conserved residue domains.

All individuals reported onset in infancy of recurrent bacterial/ fungal/ viral infections leading to bronchiectasis and poor T-cell proliferation.

Treatment: prophylactic antibiotics, IVIG, BMT.

Non-genetic confirmatory testing: no
Sources: Expert list
BabyScreen+ newborn screening v0.2025 MAGT1 Zornitza Stark Marked gene: MAGT1 as ready
BabyScreen+ newborn screening v0.2025 MAGT1 Zornitza Stark Gene: magt1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2025 MAGT1 Zornitza Stark Classified gene: MAGT1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2025 MAGT1 Zornitza Stark Gene: magt1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2024 MAGT1 Zornitza Stark gene: MAGT1 was added
gene: MAGT1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: MAGT1.
Mode of inheritance for gene: MAGT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MAGT1 were set to 31036665; 31714901
Phenotypes for gene: MAGT1 were set to Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (MIM# 300853)
Review for gene: MAGT1 was set to GREEN
Added comment: XMEN is an X-linked recessive immunodeficiency characterized by CD4 lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation. Affected individuals have chronic Epstein-Barr virus (EBV) infection and are susceptible to the development of EBV-associated B-cell lymphoproliferative disorders.

Variable age of onset, including in early childhood.

Treatment: Mg supplementation; IVIG, BMT.

Non-genetic confirmatory testing: immunoglobulin levels, T and B Lymphocyte and Natural Killer Cell Profile, Carbohydrate deficient glycosylation profile
Sources: Expert list
BabyScreen+ newborn screening v0.2023 LRBA Zornitza Stark Marked gene: LRBA as ready
BabyScreen+ newborn screening v0.2023 LRBA Zornitza Stark Gene: lrba has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2023 LRBA Zornitza Stark Classified gene: LRBA as Green List (high evidence)
BabyScreen+ newborn screening v0.2023 LRBA Zornitza Stark Gene: lrba has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2022 LRBA Zornitza Stark gene: LRBA was added
gene: LRBA was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: LRBA.
Mode of inheritance for gene: LRBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRBA were set to 22608502; 22721650; 25468195; 26206937; 33155142; 31887391
Phenotypes for gene: LRBA were set to Immunodeficiency, common variable, 8, with autoimmunity MIM# 614700
Review for gene: LRBA was set to GREEN
Added comment: Well established gene-disease association.

Generally childhood onset with recurrent infections and autoimmune phenomena.

Treatment: abatacept, BMT.

Non-genetic confirmatory testing: immunoglobulin levels.
Sources: Expert list
BabyScreen+ newborn screening v0.2021 LIG1 Zornitza Stark Marked gene: LIG1 as ready
BabyScreen+ newborn screening v0.2021 LIG1 Zornitza Stark Gene: lig1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2021 LIG1 Zornitza Stark Classified gene: LIG1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2021 LIG1 Zornitza Stark Gene: lig1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2020 LIG1 Zornitza Stark gene: LIG1 was added
gene: LIG1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: LIG1.
Mode of inheritance for gene: LIG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG1 were set to 30395541
Phenotypes for gene: LIG1 were set to Immunodeficiency 96, MIM# 619774
Review for gene: LIG1 was set to GREEN
Added comment: Established gene-disease association.

Onset is generally in early childhood.

Presents with recurrent severe infections.

Treatment: IVIG, BMT.

Non-genetic confirmatory testing: immunoglobulin levels, T and B Lymphocyte and Natural Killer Cell Profile, complete blood count
Sources: Expert list
BabyScreen+ newborn screening v0.2019 LEP Zornitza Stark Marked gene: LEP as ready
BabyScreen+ newborn screening v0.2019 LEP Zornitza Stark Gene: lep has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2019 LEP Zornitza Stark Classified gene: LEP as Green List (high evidence)
BabyScreen+ newborn screening v0.2019 LEP Zornitza Stark Gene: lep has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2018 LEP Zornitza Stark gene: LEP was added
gene: LEP was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: LEP.
Mode of inheritance for gene: LEP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LEP were set to 26567097
Phenotypes for gene: LEP were set to Obesity, morbid, due to leptin deficiency (MIM#614962)
Review for gene: LEP was set to GREEN
Added comment: Established gene-disease association.

Onset is in infancy/early childhood. Similar disorders included.

Treatment: metreleptin.

Non-genetic confirmatory testing: leptin level.
Sources: Expert list
BabyScreen+ newborn screening v0.2017 JAGN1 Zornitza Stark Marked gene: JAGN1 as ready
BabyScreen+ newborn screening v0.2017 JAGN1 Zornitza Stark Gene: jagn1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2017 JAGN1 Zornitza Stark Classified gene: JAGN1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2017 JAGN1 Zornitza Stark Gene: jagn1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2016 JAGN1 Zornitza Stark gene: JAGN1 was added
gene: JAGN1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: JAGN1.
Mode of inheritance for gene: JAGN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAGN1 were set to 25129144
Phenotypes for gene: JAGN1 were set to Neutropenia, severe congenital, 6, autosomal recessive, MIM# 616022
Review for gene: JAGN1 was set to GREEN
Added comment: Established gene-disease association.

Typically presents in early childhood with severe infections.

Treatment: G-CSF, BMT.

Non-genetic confirmatory testing: complete blood count, bone marrow aspiration and biopsy
Sources: Expert list
BabyScreen+ newborn screening v0.2015 TNFRSF13C Zornitza Stark Marked gene: TNFRSF13C as ready
BabyScreen+ newborn screening v0.2015 TNFRSF13C Zornitza Stark Gene: tnfrsf13c has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2015 TNFRSF13C Zornitza Stark Classified gene: TNFRSF13C as Red List (low evidence)
BabyScreen+ newborn screening v0.2015 TNFRSF13C Zornitza Stark Gene: tnfrsf13c has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.2014 ITK Zornitza Stark Marked gene: ITK as ready
BabyScreen+ newborn screening v0.2014 ITK Zornitza Stark Gene: itk has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2014 ITK Zornitza Stark Classified gene: ITK as Green List (high evidence)
BabyScreen+ newborn screening v0.2014 ITK Zornitza Stark Gene: itk has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2013 ITK Zornitza Stark gene: ITK was added
gene: ITK was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: ITK.
Mode of inheritance for gene: ITK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITK were set to Lymphoproliferative syndrome 1, MIM# 613011
Review for gene: ITK was set to GREEN
Added comment: 7 individuals from 5 unrelated families reported homozygous (missense/ nonsense) ITK variants consistent with Lymphoproliferative syndrome phenotype. Triggered by EBV infection.

Two ITK-deficient mouse models demonstrated reduced T cells (CD4+), causing decreased CD4 to CD8 ratio.

Patients displayed early onset of features typically including fever, lymphadenopathy, autoimmune disorders, low immunoglobulins and high EBV viral load.

Fatal without BMT.

Non-genetic confirmatory testing: immunoglobulin levels, T and B Lymphocyte and Natural Killer Cell Profile.
Sources: Expert list
BabyScreen+ newborn screening v0.2012 IRS4 Zornitza Stark changed review comment from: Nongoitrous congenital hypothyroidism-9 (CHNG9) is characterized by a small thyroid gland with low free T4 (FT4) levels and inappropriately normal levels of thyroid-stimulating hormone (TSH). Five unrelated families reported.

Most identified through standard NBS.
Sources: Expert list; to: Nongoitrous congenital hypothyroidism-9 (CHNG9) is characterized by a small thyroid gland with low free T4 (FT4) levels and inappropriately normal levels of thyroid-stimulating hormone (TSH). Five unrelated families reported.

Most identified through standard NBS.

Treatment: thyroxine.
Sources: Expert list
BabyScreen+ newborn screening v0.2012 IRS4 Zornitza Stark Marked gene: IRS4 as ready
BabyScreen+ newborn screening v0.2012 IRS4 Zornitza Stark Gene: irs4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2012 IRS4 Zornitza Stark Classified gene: IRS4 as Green List (high evidence)
BabyScreen+ newborn screening v0.2012 IRS4 Zornitza Stark Gene: irs4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2011 IRS4 Zornitza Stark gene: IRS4 was added
gene: IRS4 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: IRS4.
Mode of inheritance for gene: IRS4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IRS4 were set to 30061370
Phenotypes for gene: IRS4 were set to Hypothyroidism, congenital, nongoitrous, 9, MIM# 301035
Review for gene: IRS4 was set to GREEN
Added comment: Nongoitrous congenital hypothyroidism-9 (CHNG9) is characterized by a small thyroid gland with low free T4 (FT4) levels and inappropriately normal levels of thyroid-stimulating hormone (TSH). Five unrelated families reported.

Most identified through standard NBS.
Sources: Expert list
BabyScreen+ newborn screening v0.2010 TNFRSF13C Lilian Downie gene: TNFRSF13C was added
gene: TNFRSF13C was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TNFRSF13C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFRSF13C were set to PMID: 19666484, PMID: 27250108, PMID: 18025937
Phenotypes for gene: TNFRSF13C were set to Immunodeficiency, common variable, 4 MIM#613494
Review for gene: TNFRSF13C was set to RED
Added comment: Amber in our mendeliome
Later childhood or adult onset.
BAFFR deficiency in humans is characterized by very few circulating B cells, very low IgM and IgG serum concentrations but normal or high IgA levels.
Sources: Expert list
BabyScreen+ newborn screening v0.2010 IL36RN Zornitza Stark Marked gene: IL36RN as ready
BabyScreen+ newborn screening v0.2010 IL36RN Zornitza Stark Gene: il36rn has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2010 IL36RN Zornitza Stark Classified gene: IL36RN as Green List (high evidence)
BabyScreen+ newborn screening v0.2010 IL36RN Zornitza Stark Gene: il36rn has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2009 IL36RN Zornitza Stark gene: IL36RN was added
gene: IL36RN was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IL36RN.
Mode of inheritance for gene: IL36RN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL36RN were set to 31286990
Phenotypes for gene: IL36RN were set to Psoriasis 14, pustular, MIM# 614204
Review for gene: IL36RN was set to GREEN
Added comment: Generalized pustular psoriasis (GPP) is a life-threatening disease characterized by sudden, repeated episodes of high-grade fever, generalized rash, and disseminated pustules, with hyperleukocytosis and elevated serum levels of C-reactive protein.

Variable age of onset but predominantly in infancy/early childhood.

Treatment: ustekinumab, secukinumab, etanercept.
Sources: Expert list
BabyScreen+ newborn screening v0.2008 IL2RA Zornitza Stark Marked gene: IL2RA as ready
BabyScreen+ newborn screening v0.2008 IL2RA Zornitza Stark Gene: il2ra has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2008 IL2RA Zornitza Stark Classified gene: IL2RA as Green List (high evidence)
BabyScreen+ newborn screening v0.2008 IL2RA Zornitza Stark Gene: il2ra has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2007 IL2RA Zornitza Stark gene: IL2RA was added
gene: IL2RA was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IL2RA.
Mode of inheritance for gene: IL2RA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IL2RA were set to Immunodeficiency 41 with lymphoproliferation and autoimmunity, MIM# 606367
Review for gene: IL2RA was set to GREEN
Added comment: Immunodeficiency-41 is a disorder of immune dysregulation. Affected individuals present in infancy with recurrent viral, fungal, and bacterial infections, lymphadenopathy, and variable autoimmune features, such as autoimmune enteropathy and eczematous skin lesions. Immunologic studies show a defect in T-cell regulation.

At least 4 unrelated families reported.

Treatment: rapamycin, bone marrow transplant.

Confirmatory non-genetic testing: flow cytometric analysis.
Sources: Expert list
BabyScreen+ newborn screening v0.2006 IL21R Zornitza Stark Marked gene: IL21R as ready
BabyScreen+ newborn screening v0.2006 IL21R Zornitza Stark Gene: il21r has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2006 IL21R Zornitza Stark Classified gene: IL21R as Green List (high evidence)
BabyScreen+ newborn screening v0.2006 IL21R Zornitza Stark Gene: il21r has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2005 IL21R Zornitza Stark gene: IL21R was added
gene: IL21R was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IL21R.
Mode of inheritance for gene: IL21R was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IL21R were set to Immunodeficiency 56, MIM# 615207
Review for gene: IL21R was set to GREEN
Added comment: Biallelic inactivating mutations in IL21R causes a combined immunodeficiency that is often complicated by cryptosporidium infections.

More than 20 individuals reported. Recent series of 13 individuals: the main clinical manifestations were recurrent bacterial (84.6%), fungal (46.2%), and viral (38.5%) infections; cryptosporidiosis-associated cholangitis (46.2%); and asthma (23.1%). Inflammatory skin diseases (15.3%) and recurrent anaphylaxis (7.9%) constitute novel phenotypes of this combined immunodeficiency. Most patients exhibited hypogammaglobulinaemia and reduced proportions of memory B cells, circulating T follicular helper cells, MAIT cells and terminally differentiated NK cells. However, IgE levels were elevated in 50% of IL-21R-deficient patients.

Onset: infancy/early childhood.

Treatment: BMT.

Non-genetic confirmatory testing: immunoglobulin levels.
Sources: Expert list
BabyScreen+ newborn screening v0.2004 IL1RN Zornitza Stark Marked gene: IL1RN as ready
BabyScreen+ newborn screening v0.2004 IL1RN Zornitza Stark Gene: il1rn has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2004 IL1RN Zornitza Stark Classified gene: IL1RN as Green List (high evidence)
BabyScreen+ newborn screening v0.2004 IL1RN Zornitza Stark Gene: il1rn has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2003 IL1RN Zornitza Stark gene: IL1RN was added
gene: IL1RN was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IL1RN.
Mode of inheritance for gene: IL1RN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IL1RN were set to Interleukin 1 receptor antagonist deficiency, MIM# 612852
Review for gene: IL1RN was set to GREEN
Added comment: Severe immunodeficiency, onset in infancy. Multi-system involvement, can be fatal if untreated.

Treatment: anakinra, etanercept, methotrexate, corticosteroid
Sources: Expert list
BabyScreen+ newborn screening v0.2002 IKZF1 Zornitza Stark Marked gene: IKZF1 as ready
BabyScreen+ newborn screening v0.2002 IKZF1 Zornitza Stark Gene: ikzf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2002 IKZF1 Zornitza Stark Classified gene: IKZF1 as Green List (high evidence)
BabyScreen+ newborn screening v0.2002 IKZF1 Zornitza Stark Gene: ikzf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2001 IKZF1 Zornitza Stark Tag treatable tag was added to gene: IKZF1.
Tag immunological tag was added to gene: IKZF1.
BabyScreen+ newborn screening v0.2001 IKZF1 Zornitza Stark edited their review of gene: IKZF1: Changed rating: GREEN
BabyScreen+ newborn screening v0.2001 IKZF1 Zornitza Stark gene: IKZF1 was added
gene: IKZF1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: IKZF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: IKZF1 were set to Immunodeficiency, common variable, 13 MIM# 616873
Added comment: Over 25 individuals from 9 unrelated families with variants in IKZF1 displaying Immunodeficiency; three mouse models Heterozygous missense, frameshift and deletion variants in IKZF1 gene resulting in loss or alteration of a zinc finger DNA contact site cause LoF. Typically presents with recurrent bacterial respiratory infections, hypogammaglobulinaemia and low Ig levels; variable age of onset.

PMID 35333544: Eight individuals harboring heterozygous IKZF1R183H or IKZF1R183C variants associated with GOF effects reported. The clinical phenotypes and pathophysiology associated with IKZF1R183H/C differ from those of previously reported patients with IKZF1HI, IKZF1DN, and IKZF1DD and should therefore be considered as a novel IKAROS-associated disease entity. This condition is characterized by immune dysregulation manifestations including inflammation, autoimmunity, atopy, and polyclonal PC proliferation.

Included primarily for LoF phenotype.

Treatment: IVIG and BMT.

Non-genetic confirmatory testing: immunoglobulin levels
Sources: Expert list
BabyScreen+ newborn screening v0.2000 IKBKB Zornitza Stark changed review comment from: Primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinaemia with relatively normal numbers of B and T cells.

Treatment: bone marrow transplant.
Sources: Expert list; to: Primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinaemia with relatively normal numbers of B and T cells.

Treatment: bone marrow transplant.

Limited evidence for mono-allelic disease.
Sources: Expert list
BabyScreen+ newborn screening v0.2000 IKBKB Zornitza Stark Marked gene: IKBKB as ready
BabyScreen+ newborn screening v0.2000 IKBKB Zornitza Stark Gene: ikbkb has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.2000 IKBKB Zornitza Stark Classified gene: IKBKB as Green List (high evidence)
BabyScreen+ newborn screening v0.2000 IKBKB Zornitza Stark Gene: ikbkb has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1999 IKBKB Zornitza Stark gene: IKBKB was added
gene: IKBKB was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IKBKB.
Mode of inheritance for gene: IKBKB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IKBKB were set to Immunodeficiency 15B, MIM# 615592
Review for gene: IKBKB was set to GREEN
Added comment: Primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinaemia with relatively normal numbers of B and T cells.

Treatment: bone marrow transplant.
Sources: Expert list
BabyScreen+ newborn screening v0.1998 IFNGR2 Zornitza Stark Marked gene: IFNGR2 as ready
BabyScreen+ newborn screening v0.1998 IFNGR2 Zornitza Stark Gene: ifngr2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1998 IFNGR2 Zornitza Stark Classified gene: IFNGR2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1998 IFNGR2 Zornitza Stark Gene: ifngr2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1997 IFNGR2 Zornitza Stark gene: IFNGR2 was added
gene: IFNGR2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IFNGR2.
Mode of inheritance for gene: IFNGR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IFNGR2 were set to Immunodeficiency 28, mycobacteriosis, MIM# 614889
Review for gene: IFNGR2 was set to AMBER
Added comment: At least 5 unrelated families reported.

Commonest trigger is BCG vaccination, which is not part of the routine schedule in Australia, therefore exclude.

Treatment: BMT; avoidance of BCG.
Sources: Expert list
BabyScreen+ newborn screening v0.1996 IFNGR1 Zornitza Stark Marked gene: IFNGR1 as ready
BabyScreen+ newborn screening v0.1996 IFNGR1 Zornitza Stark Gene: ifngr1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1996 IFNGR1 Zornitza Stark Classified gene: IFNGR1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1996 IFNGR1 Zornitza Stark Gene: ifngr1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1995 IFNGR1 Zornitza Stark Tag treatable tag was added to gene: IFNGR1.
Tag immunological tag was added to gene: IFNGR1.
BabyScreen+ newborn screening v0.1995 IFNGR1 Zornitza Stark gene: IFNGR1 was added
gene: IFNGR1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: IFNGR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: IFNGR1 were set to Immunodeficiency 27A, mycobacteriosis, AR, MIM# 209950; Immunodeficiency 27B, mycobacteriosis, AD, MIM# 615978
Review for gene: IFNGR1 was set to AMBER
Added comment: Variable age of onset. Most common precipitant is BCG vaccination, which is not part of the routine schedule in Australia, therefore exclude.

Treatment: BMT; avoidance of BCG.
Sources: Expert list
BabyScreen+ newborn screening v0.1994 IFITM5 Zornitza Stark Marked gene: IFITM5 as ready
BabyScreen+ newborn screening v0.1994 IFITM5 Zornitza Stark Gene: ifitm5 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1994 IFITM5 Zornitza Stark Classified gene: IFITM5 as Green List (high evidence)
BabyScreen+ newborn screening v0.1994 IFITM5 Zornitza Stark Gene: ifitm5 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1993 IFITM5 Zornitza Stark gene: IFITM5 was added
gene: IFITM5 was added to Baby Screen+ newborn screening. Sources: Expert list
5'UTR, treatable, skeletal tags were added to gene: IFITM5.
Mode of inheritance for gene: IFITM5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IFITM5 were set to 22863190; 22863195; 32383316; 24519609
Phenotypes for gene: IFITM5 were set to Osteogenesis imperfecta, type V MIM#610967
Review for gene: IFITM5 was set to GREEN
Added comment: A recurrent c.-14C>T variant has been reported in many patients with type V OI. It introduces an alternative in-frame start codon upstream that is stronger than the reference start codon in transfected HEK cells (PMIDs: 22863190, 22863195). However, the effect of mutant protein (5 amino acids longer) remains unknown but neomorphic mechanism is a widely accepted hypothesis (PMIDs: 25251575, 32383316).

Variable severity, including within families. However, severe perinatal presentations reported.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
BabyScreen+ newborn screening v0.1992 ICOS Zornitza Stark Marked gene: ICOS as ready
BabyScreen+ newborn screening v0.1992 ICOS Zornitza Stark Gene: icos has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1992 ICOS Zornitza Stark Classified gene: ICOS as Green List (high evidence)
BabyScreen+ newborn screening v0.1992 ICOS Zornitza Stark Gene: icos has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1991 ICOS Zornitza Stark gene: ICOS was added
gene: ICOS was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: ICOS.
Mode of inheritance for gene: ICOS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ICOS were set to Immunodeficiency, common variable, 1 MIM# 607594
Review for gene: ICOS was set to GREEN
Added comment: 15 affected individuals from 8 unrelated families reported with ICOS variants and displayed immunodeficiency, common variable, 1 phenotype; three mouse models.

Homozygous and compound heterozygous deletion and missense variants, with the most frequent variant being a 442 nucleotide deletion.

Patients typically presented with recurrent bacterial respiratory & gastrointestinal infections and low IgG/IgA.

Congenital onset.

Treatment: replacement immunoglobulin treatment, bone marrow transplant.

Non-genetic confirmatory testing: immunoglobulin levels.
Sources: Expert list
BabyScreen+ newborn screening v0.1990 IARS Zornitza Stark Marked gene: IARS as ready
BabyScreen+ newborn screening v0.1990 IARS Zornitza Stark Gene: iars has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1990 IARS Zornitza Stark Classified gene: IARS as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1990 IARS Zornitza Stark Gene: iars has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1989 IARS Zornitza Stark Tag treatable tag was added to gene: IARS.
Tag metabolic tag was added to gene: IARS.
BabyScreen+ newborn screening v0.1989 IARS Zornitza Stark gene: IARS was added
gene: IARS was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: IARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS were set to 27426735; 34194004
Phenotypes for gene: IARS were set to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM#617093
Review for gene: IARS was set to AMBER
Added comment: Established gene-disease association.

Congenital, multi-system metabolic disorder.

N=1 study of Isoleucine supplementation and protein fortification (2.5mg/kg/day, during illness 3.5 g/kg/day) with some clinical improvement.
Sources: Expert list
BabyScreen+ newborn screening v0.1988 TNFRSF1A Zornitza Stark Marked gene: TNFRSF1A as ready
BabyScreen+ newborn screening v0.1988 TNFRSF1A Zornitza Stark Gene: tnfrsf1a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1988 TNFRSF1A Zornitza Stark Classified gene: TNFRSF1A as Red List (low evidence)
BabyScreen+ newborn screening v0.1988 TNFRSF1A Zornitza Stark Gene: tnfrsf1a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1987 TOP2B Zornitza Stark Marked gene: TOP2B as ready
BabyScreen+ newborn screening v0.1987 TOP2B Zornitza Stark Gene: top2b has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1987 TOP2B Zornitza Stark Classified gene: TOP2B as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1987 TOP2B Zornitza Stark Gene: top2b has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1986 TOP2B Zornitza Stark reviewed gene: TOP2B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: B-cell immunodeficiency, distal limb anomalies, and urogenital malformations MIM#609296; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1986 TPK1 Zornitza Stark Marked gene: TPK1 as ready
BabyScreen+ newborn screening v0.1986 TPK1 Zornitza Stark Gene: tpk1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1986 TPK1 Zornitza Stark Classified gene: TPK1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1986 TPK1 Zornitza Stark Gene: tpk1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1985 TPK1 Zornitza Stark Tag treatable tag was added to gene: TPK1.
Tag metabolic tag was added to gene: TPK1.
BabyScreen+ newborn screening v0.1985 TRNT1 Zornitza Stark Marked gene: TRNT1 as ready
BabyScreen+ newborn screening v0.1985 TRNT1 Zornitza Stark Gene: trnt1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1985 TRNT1 Zornitza Stark Classified gene: TRNT1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1985 TRNT1 Zornitza Stark Gene: trnt1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1984 TRNT1 Zornitza Stark Tag treatable tag was added to gene: TRNT1.
Tag immunological tag was added to gene: TRNT1.
BabyScreen+ newborn screening v0.1984 TRNT1 Zornitza Stark reviewed gene: TRNT1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay MIM#616084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1984 TRPM6 Zornitza Stark Marked gene: TRPM6 as ready
BabyScreen+ newborn screening v0.1984 TRPM6 Zornitza Stark Gene: trpm6 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1984 TRPM6 Zornitza Stark Classified gene: TRPM6 as Green List (high evidence)
BabyScreen+ newborn screening v0.1984 TRPM6 Zornitza Stark Gene: trpm6 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1983 TRPM6 Zornitza Stark Tag treatable tag was added to gene: TRPM6.
Tag endocrine tag was added to gene: TRPM6.
BabyScreen+ newborn screening v0.1983 UCP2 Zornitza Stark Marked gene: UCP2 as ready
BabyScreen+ newborn screening v0.1983 UCP2 Zornitza Stark Gene: ucp2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1983 UCP2 Zornitza Stark Publications for gene: UCP2 were set to
BabyScreen+ newborn screening v0.1982 TNFRSF1A Lilian Downie gene: TNFRSF1A was added
gene: TNFRSF1A was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TNFRSF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNFRSF1A were set to PMID: 11175303, PMID: 32066461, PMID: 29773275, PMID: 32831641
Phenotypes for gene: TNFRSF1A were set to Periodic fever, familial MIM#142680
Penetrance for gene: TNFRSF1A were set to Incomplete
Review for gene: TNFRSF1A was set to RED
Added comment: Strong gene disease association
Childhood onset but age not consistently under 5 and cases of adult onset
reports of variable penetrance
Rx
NSAIDs, corticosteroids, Etanercept , anakinra, canakinumab, tocilizumab

because there is no non-molecular confirmatory test I think should be red for variability of age of onset and severity of symptoms.
Sources: Expert list
BabyScreen+ newborn screening v0.1982 TOP2B Lilian Downie gene: TOP2B was added
gene: TOP2B was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TOP2B were set to PMID: 31409799, PMID: 35063500, PMID: 32128574, PMID: 33459963
Phenotypes for gene: TOP2B were set to B-cell immunodeficiency, distal limb anomalies, and urogenital malformations MIM#609296
Review for gene: TOP2B was set to AMBER
Added comment: congenital onset
humoral immunodeficiency with undetectable B cells, distal limb anomalies, dysmorphic facial features, and urogenital malformations

Treatment immunoglobulin (only partially treats phenotype) no literature for evidence around immunoglobulin treatment.

Suggest RED but maybe discuss with immunologist?
Sources: Expert list
BabyScreen+ newborn screening v0.1982 TPK1 Lilian Downie gene: TPK1 was added
gene: TPK1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TPK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPK1 were set to PMID: 33086386, 32679198, 22152682, PMID: 33231275
Phenotypes for gene: TPK1 were set to Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) MIM#614458
Review for gene: TPK1 was set to GREEN
Added comment: Strong gene disease association
Variable age of onset but always under 5years

Thiamine metabolism dysfunction syndrome-5 (THMD5) is an autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits (Mayr et al., 2011).

Biotin and thiamine therapy - newer evidence (2021) suggests early thiamine therapy may prevent any neurologic deficits.
Sources: Expert list
BabyScreen+ newborn screening v0.1982 TRNT1 Lilian Downie gene: TRNT1 was added
gene: TRNT1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TRNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRNT1 were set to PMID: 25193871, PMID: 23553769, PMID: 33936027, PMID: 26494905
Phenotypes for gene: TRNT1 were set to Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay MIM#616084
Review for gene: TRNT1 was set to AMBER
Added comment: Onset infancy
Strong gene disease association

Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) is an autosomal recessive syndromic disorder characterized by onset of severe sideroblastic anemia in the neonatal period or infancy. Affected individuals show delayed psychomotor development with variable neurodegeneration. Recurrent periodic fevers without an infectious etiology occur throughout infancy and childhood; immunologic work-up shows B-cell lymphopenia and hypogammaglobulinemia. Other more variable features include sensorineural hearing loss, retinitis pigmentosa, nephrocalcinosis, and cardiomyopathy. Death in the first decade may occur (summary by Wiseman et al., 2013).

Bone marrow transplant (hematopoietic stem cell transplantation (HSCT)), replacement immunoglobulin treatment

Allelic disease: Retinitis pigmentosa and erythrocytic microcytosis MIM#616959. Also AR.
DeLuca et al. (2016) concluded that hypomorphic TRNT1 mutations can cause a recessive disease that is almost entirely limited to the retina - this has teenage onset and is not treatable. can we exclude these variants?
Sources: Expert list
BabyScreen+ newborn screening v0.1982 TRPM6 Lilian Downie gene: TRPM6 was added
gene: TRPM6 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TRPM6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPM6 were set to PMID: 35903165, PMID: 18818955
Phenotypes for gene: TRPM6 were set to Hypomagnesemia 1, intestinal MIM#602014
Review for gene: TRPM6 was set to GREEN
Added comment: Hypomagnaesemia and hypocalcaemia
Hypocalcemia is a secondary consequence of parathyroid failure and parathyroid hormone resistance as a result of severe magnesium deficiency. The disease typically manifests during the first months of life with generalized convulsions or signs of increased neuromuscular excitability, such as muscle spasms or tetany. Untreated, the disease may be fatal or lead to severe neurologic damage. Treatment includes immediate administration of magnesium, usually intravenously, followed by life-long high-dose oral magnesium (review by Knoers, 2009).
Sources: Expert list
BabyScreen+ newborn screening v0.1982 UCP2 Lilian Downie reviewed gene: UCP2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 28681398, PMID: 27967291; Phenotypes: UCP2 associated hyperinsulinism; Mode of inheritance: None
BabyScreen+ newborn screening v0.1982 UNG Zornitza Stark Marked gene: UNG as ready
BabyScreen+ newborn screening v0.1982 UNG Zornitza Stark Gene: ung has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1982 UNG Zornitza Stark Classified gene: UNG as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1982 UNG Zornitza Stark Gene: ung has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1981 UNG Zornitza Stark Tag treatable tag was added to gene: UNG.
Tag immunological tag was added to gene: UNG.
BabyScreen+ newborn screening v0.1981 UNG Zornitza Stark reviewed gene: UNG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency with hyper IgM, type 5 MIM#608106; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1981 UMPS Zornitza Stark Marked gene: UMPS as ready
BabyScreen+ newborn screening v0.1981 UMPS Zornitza Stark Gene: umps has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1981 UMPS Zornitza Stark Classified gene: UMPS as Green List (high evidence)
BabyScreen+ newborn screening v0.1981 UMPS Zornitza Stark Gene: umps has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1980 UMPS Zornitza Stark Tag for review tag was added to gene: UMPS.
Tag treatable tag was added to gene: UMPS.
Tag metabolic tag was added to gene: UMPS.
BabyScreen+ newborn screening v0.1980 NLGN4X Zornitza Stark Marked gene: NLGN4X as ready
BabyScreen+ newborn screening v0.1980 NLGN4X Zornitza Stark Gene: nlgn4x has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1980 NLGN4X Zornitza Stark Phenotypes for gene: NLGN4X were changed from Autism to Intellectual developmental disorder, X-linked MIM#300495
BabyScreen+ newborn screening v0.1979 NLGN4X Zornitza Stark Mode of inheritance for gene: NLGN4X was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1978 NLGN4X Zornitza Stark reviewed gene: NLGN4X: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked MIM#300495; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1978 HSD11B2 Zornitza Stark Marked gene: HSD11B2 as ready
BabyScreen+ newborn screening v0.1978 HSD11B2 Zornitza Stark Gene: hsd11b2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1978 HSD11B2 Zornitza Stark Classified gene: HSD11B2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1978 HSD11B2 Zornitza Stark Gene: hsd11b2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1977 HSD11B2 Zornitza Stark gene: HSD11B2 was added
gene: HSD11B2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: HSD11B2.
Mode of inheritance for gene: HSD11B2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HSD11B2 were set to Apparent mineralocorticoid excess, MIM# 218030; MONDO:0009025
Review for gene: HSD11B2 was set to GREEN
Added comment: Apparent mineralocorticoid excess (AME) is an autosomal recessive form of low-renin hypertension associated with low aldosterone, metabolic alkalosis, hypernatremia, and hypokalemia. The disorder is due to a congenital defect in 11-beta-hydroxysteroid dehydrogenase type II (HSD11B2) activity, resulting in decreased conversion of biologically active cortisol to inactive cortisone; this defect allows cortisol to act as a ligand for the mineralocorticoid receptor, resulting in sodium retention and volume expansion. There is a favorable therapeutic response to spironolactone. More than 10 unrelated families reported.

Onset is usually in infancy or early childhood.

Non-genetic confirmatory testing: aldosterone, renin, potassium levels
Sources: Expert list
BabyScreen+ newborn screening v0.1976 HOGA1 Zornitza Stark Marked gene: HOGA1 as ready
BabyScreen+ newborn screening v0.1976 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1976 HOGA1 Zornitza Stark Classified gene: HOGA1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1976 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1975 HOGA1 Zornitza Stark gene: HOGA1 was added
gene: HOGA1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: HOGA1.
Mode of inheritance for gene: HOGA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HOGA1 were set to 20797690; 21896830; 22391140
Phenotypes for gene: HOGA1 were set to Hyperoxaluria, primary, type III MIM#613616
Review for gene: HOGA1 was set to GREEN
Added comment: Well-established association with primary hyperoxaluria type III. c.700+5G>T is a recurrent pathogenic variant in European populations (possibly founder) and has high frequency in gnomad (0.2-0.3%).

Onset in infancy, progressive multi-system disorder.

Treatment: pyridoxine, drinking large volumes, alkalinzation of urine, pyrophosphate-containing solutions, liver-kidney transplant

Non-genetic confirmatory testing: urinary oxalate
Sources: Expert list
BabyScreen+ newborn screening v0.1974 UMPS Lilian Downie changed review comment from: megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001).

Treat uridine
Very rare only 20 cases but treatable.
Sources: Expert list; to: megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001).

Better check with John who wrote the paper!! PMID: 25030255

Treat uridine
Very rare only 20 cases but treatable.
Sources: Expert list
BabyScreen+ newborn screening v0.1974 UMPS Lilian Downie gene: UMPS was added
gene: UMPS was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: UMPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UMPS were set to PMID: 9042911, PMID: 28205048, PMID: 25757096, PMID: 33489760
Phenotypes for gene: UMPS were set to Orotic aciduria MIM#258900
Review for gene: UMPS was set to GREEN
Added comment: megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001).

Treat uridine
Very rare only 20 cases but treatable.
Sources: Expert list
BabyScreen+ newborn screening v0.1974 UNG Lilian Downie gene: UNG was added
gene: UNG was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: UNG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNG were set to PubMed: 12958596, PMID: 15967827, PMID: 19202054, PMID: 16860315
Phenotypes for gene: UNG were set to Immunodeficiency with hyper IgM, type 5 MIM#608106
Review for gene: UNG was set to RED
Added comment: normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations.
susceptibility to bacterial infections, lymphoid hyperplasia
only 3 patients reported in a single paper ?
Rx immunoglobulin replacement according to Rx genes but I can't find actual papers - i don't think there is enough evidence regarding age of onset or treatability.
Sources: Expert list
BabyScreen+ newborn screening v0.1974 HELLS Zornitza Stark Marked gene: HELLS as ready
BabyScreen+ newborn screening v0.1974 HELLS Zornitza Stark Gene: hells has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1974 HELLS Zornitza Stark Classified gene: HELLS as Green List (high evidence)
BabyScreen+ newborn screening v0.1974 HELLS Zornitza Stark Gene: hells has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1973 HELLS Zornitza Stark Tag treatable tag was added to gene: HELLS.
Tag immunological tag was added to gene: HELLS.
BabyScreen+ newborn screening v0.1973 HELLS Zornitza Stark gene: HELLS was added
gene: HELLS was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: HELLS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HELLS were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 4, MIM# 616911
Review for gene: HELLS was set to GREEN
Added comment: Congenital onset.

Immunodeficiency-centromeric instability-facial anomalies syndrome-4 is characterized by recurrent infections in childhood and variable dysmorphic facial features. Laboratory studies show hypomethylation of certain chromosomal regions. Additional features, including delayed development, are variable. At least 4 unrelated families reported.

Treatment: bone marrow transplant.
Sources: Expert list
BabyScreen+ newborn screening v0.1972 USP18 Zornitza Stark Marked gene: USP18 as ready
BabyScreen+ newborn screening v0.1972 USP18 Zornitza Stark Gene: usp18 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1972 USP18 Zornitza Stark Classified gene: USP18 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1972 USP18 Zornitza Stark Gene: usp18 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1971 USP18 Zornitza Stark reviewed gene: USP18: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudo-TORCH syndrome 2 MIM#617397; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1971 VKORC1 Zornitza Stark Marked gene: VKORC1 as ready
BabyScreen+ newborn screening v0.1971 VKORC1 Zornitza Stark Gene: vkorc1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1971 VKORC1 Zornitza Stark Mode of inheritance for gene: VKORC1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1970 VKORC1 Zornitza Stark Classified gene: VKORC1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1970 VKORC1 Zornitza Stark Gene: vkorc1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1969 VKORC1 Zornitza Stark Tag treatable tag was added to gene: VKORC1.
Tag haematological tag was added to gene: VKORC1.
BabyScreen+ newborn screening v0.1969 VKORC1 Zornitza Stark reviewed gene: VKORC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Vitamin K-dependent clotting factors, combined deficiency of, 2 MIM#607473; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1969 WDR1 Zornitza Stark Marked gene: WDR1 as ready
BabyScreen+ newborn screening v0.1969 WDR1 Zornitza Stark Gene: wdr1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1969 WDR1 Zornitza Stark Classified gene: WDR1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1969 WDR1 Zornitza Stark Gene: wdr1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1968 WDR1 Zornitza Stark Tag treatable tag was added to gene: WDR1.
Tag immunological tag was added to gene: WDR1.
Tag haematological tag was added to gene: WDR1.
BabyScreen+ newborn screening v0.1968 GPIHBP1 Zornitza Stark Marked gene: GPIHBP1 as ready
BabyScreen+ newborn screening v0.1968 GPIHBP1 Zornitza Stark Gene: gpihbp1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1968 GPIHBP1 Zornitza Stark Classified gene: GPIHBP1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1968 GPIHBP1 Zornitza Stark Gene: gpihbp1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1967 GPIHBP1 Zornitza Stark Tag treatable tag was added to gene: GPIHBP1.
Tag metabolic tag was added to gene: GPIHBP1.
BabyScreen+ newborn screening v0.1967 GPIHBP1 Zornitza Stark gene: GPIHBP1 was added
gene: GPIHBP1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GPIHBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPIHBP1 were set to 31390500
Phenotypes for gene: GPIHBP1 were set to Hyperlipoproteinemia, type 1D MIM#615947; familial chylomicronemia syndrome
Review for gene: GPIHBP1 was set to GREEN
Added comment: Well-established gene-disease association.

Usually presents in childhood with episodes of abdominal pain, recurrent acute pancreatitis, eruptive cutaneous xanthomata, and hepatosplenomegaly.

Approximately 25% of affected children develop symptoms before age one year and the majority develop symptoms before age ten years; however, some individuals present for the first time during pregnancy.

Treatment: volanesorsen, dietary fat restriction

Non-genetic confirmatory testing: triglyceride level
Sources: Expert list
BabyScreen+ newborn screening v0.1966 GHRHR Zornitza Stark Marked gene: GHRHR as ready
BabyScreen+ newborn screening v0.1966 GHRHR Zornitza Stark Gene: ghrhr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1966 GHRHR Zornitza Stark Classified gene: GHRHR as Green List (high evidence)
BabyScreen+ newborn screening v0.1966 GHRHR Zornitza Stark Gene: ghrhr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1965 GHRHR Zornitza Stark Tag treatable tag was added to gene: GHRHR.
Tag endocrine tag was added to gene: GHRHR.
BabyScreen+ newborn screening v0.1965 GHRHR Zornitza Stark gene: GHRHR was added
gene: GHRHR was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GHRHR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GHRHR were set to 8528260; 10084571; 11232012
Phenotypes for gene: GHRHR were set to Growth hormone deficiency, isolated, type IV, MIM# 618157
Review for gene: GHRHR was set to GREEN
Added comment: IGHD type IV is characterized by early and severe growth failure (height SDS up to -7.4), a blunted growth hormone (GH) response to different provocation tests and low insulin-like growth factor-I and IGF-binding protein-3 concentrations, and a good response to growth hormone treatment. At least three unrelated families reported.

Non-genetic confirmatory testing: growth hormone stimulation test
Sources: Expert list
BabyScreen+ newborn screening v0.1964 GHR Zornitza Stark Marked gene: GHR as ready
BabyScreen+ newborn screening v0.1964 GHR Zornitza Stark Gene: ghr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1964 GHR Zornitza Stark Classified gene: GHR as Green List (high evidence)
BabyScreen+ newborn screening v0.1964 GHR Zornitza Stark Gene: ghr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1963 GHR Zornitza Stark Tag treatable tag was added to gene: GHR.
Tag endocrine tag was added to gene: GHR.
BabyScreen+ newborn screening v0.1963 GHR Zornitza Stark gene: GHR was added
gene: GHR was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GHR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GHR were set to Growth hormone insensitivity, partial, MIM# 604271; Laron dwarfism, MIM# 262500
Review for gene: GHR was set to GREEN
Added comment: Well established gene-disease association.

Congenital onset.

Treatment: growth hormone.

Non-genetic confirmatory testing: growth hormone stimulation test
Sources: Expert list
BabyScreen+ newborn screening v0.1962 GH1 Zornitza Stark Marked gene: GH1 as ready
BabyScreen+ newborn screening v0.1962 GH1 Zornitza Stark Gene: gh1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1962 GH1 Zornitza Stark Classified gene: GH1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1962 GH1 Zornitza Stark Gene: gh1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1961 GH1 Zornitza Stark Tag treatable tag was added to gene: GH1.
Tag endocrine tag was added to gene: GH1.
BabyScreen+ newborn screening v0.1961 GH1 Zornitza Stark gene: GH1 was added
gene: GH1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GH1 were set to Growth hormone deficiency, isolated, type IA, MIM# 262400; Growth hormone deficiency, isolated, type II, MIM# 173100; Kowarski syndrome, MIM# 262650
Review for gene: GH1 was set to GREEN
Added comment: Well established gene-disease association. Congenital onset.

Treatment: growth hormone.

Non-genetic confirmatory test: growth hormone stimulation test
Sources: Expert list
BabyScreen+ newborn screening v0.1960 GFI1 Zornitza Stark Marked gene: GFI1 as ready
BabyScreen+ newborn screening v0.1960 GFI1 Zornitza Stark Gene: gfi1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1960 GFI1 Zornitza Stark Classified gene: GFI1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1960 GFI1 Zornitza Stark Gene: gfi1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1959 GFI1 Zornitza Stark gene: GFI1 was added
gene: GFI1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GFI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GFI1 were set to 12778173; 20560965; 11810106; 22684987
Phenotypes for gene: GFI1 were set to Neutropenia, severe congenital 2, autosomal dominant, MIM# 613107
Review for gene: GFI1 was set to GREEN
Added comment: At least three unrelated families reported, and supportive functional data.

Severe congenital immunodeficiency.

Treatment: granulocyte colony-stimulating factor (G-CSF), Bone marrow transplant

Non-genetic confirmatory testing: FBE.
Sources: Expert list
BabyScreen+ newborn screening v0.1958 USP18 Lilian Downie gene: USP18 was added
gene: USP18 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: USP18 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP18 were set to PMID: 31940699, 27325888, 12833411
Phenotypes for gene: USP18 were set to Pseudo-TORCH syndrome 2 MIM#617397
Review for gene: USP18 was set to AMBER
Added comment: antenatal onset of intracranial hemorrhage, calcification, brain malformations, liver dysfunction, and often thrombocytopenia. Affected individuals tend to have respiratory insufficiency and seizures, and die in infancy. The phenotype resembles the sequelae of intrauterine infection, but there is no evidence of an infectious agent. The disorder results from inappropriate activation of the interferon (IFN) immunologic pathway

Treatment Ruxolitinib (single patient only) - is a single patient with successful treatment enough?
Sources: Expert list
BabyScreen+ newborn screening v0.1958 VKORC1 Lilian Downie gene: VKORC1 was added
gene: VKORC1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: VKORC1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: VKORC1 were set to PMID:14765194, PMID: 26287237
Phenotypes for gene: VKORC1 were set to Vitamin K-dependent clotting factors, combined deficiency of, 2 MIM#607473
Review for gene: VKORC1 was set to AMBER
Added comment: Risk of intracranial haemmorhage in first weeks of life
Treatable with vitamin K
See below summary - feels like should be green for that homozygous mutation but not sure how to manage the gene overall? not report other variants?
Monoallelic - warfarin resistance

There is only one mutation known to result in the VKCFD2 phenotype. VKORC1:p.Arg98Trp causes diminished vitamin K epoxide reductase (VKOR) activity compared to that of the wild-type enzyme [15]. VKCFD2 patients exhibit severely diminished activities for the VKD coagulation factors and suffer spontaneous or surgery/injury induced bleeding episodes [16,17]. In addition to this haemorrhagic phenotype, abnormalities in epiphyseal growth have been reported in one case [18]. This phenotype is very rare. Worldwide, there are only four unrelated families known to be affected with VKCFD2 [16,17,18].
Sources: Expert list
BabyScreen+ newborn screening v0.1958 WDR1 Lilian Downie gene: WDR1 was added
gene: WDR1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: WDR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR1 were set to PMID: 32960541, 27994071, 27557945
Phenotypes for gene: WDR1 were set to Periodic fever, immunodeficiency, and thrombocytopenia syndrome MIM#150550
Review for gene: WDR1 was set to GREEN
Added comment: Strong gene disease association
Phenotype is early onset immunodeficiency with infections ++ and severe stomatitis
Treatable with bone marrow transplant.
Sources: Expert list
BabyScreen+ newborn screening v0.1958 WDR72 Zornitza Stark Marked gene: WDR72 as ready
BabyScreen+ newborn screening v0.1958 WDR72 Zornitza Stark Gene: wdr72 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1958 WDR72 Zornitza Stark Phenotypes for gene: WDR72 were changed from Distal renal tubular acidosis to Amelogenesis imperfecta, type IIA3, MIM# 613211; Distal RTA MONDO:0015827
BabyScreen+ newborn screening v0.1957 WDR72 Zornitza Stark Classified gene: WDR72 as Green List (high evidence)
BabyScreen+ newborn screening v0.1957 WDR72 Zornitza Stark Gene: wdr72 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1956 WDR72 Zornitza Stark Tag treatable tag was added to gene: WDR72.
Tag renal tag was added to gene: WDR72.
BabyScreen+ newborn screening v0.1956 WDR72 Zornitza Stark reviewed gene: WDR72: Rating: GREEN; Mode of pathogenicity: None; Publications: 30028003; Phenotypes: Amelogenesis imperfecta, type IIA3, MIM# 613211, Distal RTA MONDO:0015827; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1956 WIPF1 Zornitza Stark Marked gene: WIPF1 as ready
BabyScreen+ newborn screening v0.1956 WIPF1 Zornitza Stark Gene: wipf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1956 WIPF1 Zornitza Stark Classified gene: WIPF1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1956 WIPF1 Zornitza Stark Gene: wipf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1955 WIPF1 Zornitza Stark Tag treatable tag was added to gene: WIPF1.
Tag immunological tag was added to gene: WIPF1.
Tag haematological tag was added to gene: WIPF1.
BabyScreen+ newborn screening v0.1955 WNK4 Zornitza Stark Marked gene: WNK4 as ready
BabyScreen+ newborn screening v0.1955 WNK4 Zornitza Stark Gene: wnk4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1955 WNK4 Zornitza Stark Classified gene: WNK4 as Green List (high evidence)
BabyScreen+ newborn screening v0.1955 WNK4 Zornitza Stark Gene: wnk4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1954 WNK4 Zornitza Stark Tag treatable tag was added to gene: WNK4.
Tag endocrine tag was added to gene: WNK4.
BabyScreen+ newborn screening v0.1954 ZBTB24 Zornitza Stark Marked gene: ZBTB24 as ready
BabyScreen+ newborn screening v0.1954 ZBTB24 Zornitza Stark Gene: zbtb24 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1954 ZBTB24 Zornitza Stark Classified gene: ZBTB24 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1954 ZBTB24 Zornitza Stark Gene: zbtb24 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1953 ZBTB24 Zornitza Stark Tag treatable tag was added to gene: ZBTB24.
Tag immunological tag was added to gene: ZBTB24.
BabyScreen+ newborn screening v0.1953 ZBTB24 Zornitza Stark reviewed gene: ZBTB24: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency-centromeric instability-facial anomalies syndrome 2 MIM#614069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1953 ZNF143 Zornitza Stark Marked gene: ZNF143 as ready
BabyScreen+ newborn screening v0.1953 ZNF143 Zornitza Stark Gene: znf143 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1953 ZNF143 Zornitza Stark Classified gene: ZNF143 as Red List (low evidence)
BabyScreen+ newborn screening v0.1953 ZNF143 Zornitza Stark Gene: znf143 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1952 ZNF143 Zornitza Stark reviewed gene: ZNF143: Rating: RED; Mode of pathogenicity: None; Publications: 27349184; Phenotypes: Combined methylmalonic acidemia and homocystinuria, cblX like 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1952 WDR72 Lilian Downie gene: WDR72 was added
gene: WDR72 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: WDR72 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR72 were set to PMID: 30028003, PMID: 30779877, PMID:36836560, PMID: 33033857
Phenotypes for gene: WDR72 were set to Distal renal tubular acidosis
Review for gene: WDR72 was set to GREEN
Added comment: Amelogenesis imperecta - thickened and disoloured dental enamal with RTA
Reduced penetrance or variable expression? Some patients only have the tooth phenotype...
Presents with polyuria and growth restriction
Treat with oral alkali replacement therapy, potassium chloride
Sources: Expert list
BabyScreen+ newborn screening v0.1952 WIPF1 Lilian Downie gene: WIPF1 was added
gene: WIPF1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: WIPF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WIPF1 were set to PMID: 27742395, PMID: 30450104, PMID: 22231303
Phenotypes for gene: WIPF1 were set to Wiskott-Aldrich syndrome 2 MIM#614493
Review for gene: WIPF1 was set to GREEN
Added comment: Infant onset
recurrent infections, thrombycytopenia and eczema
Immunology testing to correlate
Treatment/cure with bone marrow transplant
Sources: Expert list
BabyScreen+ newborn screening v0.1952 WNK4 Lilian Downie gene: WNK4 was added
gene: WNK4 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: WNK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WNK4 were set to PMID: 22073419, PMID: 31795491, PMID: 10869238,
Phenotypes for gene: WNK4 were set to Pseudohypoaldosteronism, type IIB MIM#614491
Review for gene: WNK4 was set to GREEN
Added comment: Hyperkalaemia and hypertension
Hypercalciuria
Hypocalcaemia
Decreased bone mineral density
Renal calcium stones
Treatable with thiazide diuretics
Variable age of onset from infancy to adulthood but highly effective treatment so leaning toward include.
Sources: Expert list
BabyScreen+ newborn screening v0.1952 ZBTB24 Lilian Downie gene: ZBTB24 was added
gene: ZBTB24 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: ZBTB24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZBTB24 were set to PMID: 28128455, 21906047, 21596365, 23486536
Phenotypes for gene: ZBTB24 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 2 MIM#614069
Review for gene: ZBTB24 was set to AMBER
Added comment: INfant onset
Agammaglobulinemia, facial anomalies, and mental retardation. Facial anomalies included broad, flat nasal bridge, hypertelorism, and epicanthal folds.
Treat immunoglobulin and bone marrow transplant however, this only treats the immune deficiency
Consider exclusion due to untreatable ID phenotype?
Sources: Expert list
BabyScreen+ newborn screening v0.1952 ZNF143 Lilian Downie gene: ZNF143 was added
gene: ZNF143 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: ZNF143 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF143 were set to PMID: 20301503, PMID: 27349184
Phenotypes for gene: ZNF143 were set to Combined methylmalonic acidemia and homocystinuria, cblX like 1
Review for gene: ZNF143 was set to RED
Added comment: Not in our mendeliome
Single case
Sources: Expert list
BabyScreen+ newborn screening v0.1952 FOLR1 Zornitza Stark Marked gene: FOLR1 as ready
BabyScreen+ newborn screening v0.1952 FOLR1 Zornitza Stark Gene: folr1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1952 FOLR1 Zornitza Stark Classified gene: FOLR1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1952 FOLR1 Zornitza Stark Gene: folr1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1951 FOLR1 Zornitza Stark gene: FOLR1 was added
gene: FOLR1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: FOLR1.
Mode of inheritance for gene: FOLR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOLR1 were set to 19732866; 30420205; 27743887
Phenotypes for gene: FOLR1 were set to Neurodegeneration due to cerebral folate transport deficiency, MIM# 613068
Review for gene: FOLR1 was set to GREEN
Added comment: Folate is a neurotransmitter precursor. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy, and leukodystrophy. Recognition and diagnosis of this disorder is critical because folinic acid therapy can reverse the clinical symptoms and improve brain abnormalities and function.

Treatment: folinic acid

Non-genetic confirmatory testing: cerebrospinal fluid 5-methyltetrahydrofolate level
Sources: Expert list
BabyScreen+ newborn screening v0.1950 FCHO1 Zornitza Stark Marked gene: FCHO1 as ready
BabyScreen+ newborn screening v0.1950 FCHO1 Zornitza Stark Gene: fcho1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1950 FCHO1 Zornitza Stark Classified gene: FCHO1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1950 FCHO1 Zornitza Stark Gene: fcho1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1949 FCHO1 Zornitza Stark edited their review of gene: FCHO1: Changed rating: GREEN
BabyScreen+ newborn screening v0.1949 FCHO1 Zornitza Stark gene: FCHO1 was added
gene: FCHO1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: FCHO1.
Mode of inheritance for gene: FCHO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FCHO1 were set to 32098969; 30822429
Phenotypes for gene: FCHO1 were set to Immunodeficiency 76, MIM# 619164
Added comment: More than 10 affected individuals with bi-allelic variants in this gene reported. Functional data.

Immunodeficiency-76 (IMD76) is an autosomal recessive primary immunologic disorder characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Laboratory studies show T-cell lymphopenia and may show variable B-cell or immunoglobulin abnormalities. More variable features found in some patients include lymphoma and neurologic features.

Treatment: bone marrow transplant.

Non-genetic confirmatory testing: T and B Lymphocyte and Natural Killer Cell Profile, immunoglobulin levels
Sources: Expert list
BabyScreen+ newborn screening v0.1948 FAM111A Zornitza Stark Marked gene: FAM111A as ready
BabyScreen+ newborn screening v0.1948 FAM111A Zornitza Stark Gene: fam111a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1948 FAM111A Zornitza Stark Classified gene: FAM111A as Green List (high evidence)
BabyScreen+ newborn screening v0.1948 FAM111A Zornitza Stark Gene: fam111a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1947 FAM111A Zornitza Stark Tag treatable tag was added to gene: FAM111A.
Tag skeletal tag was added to gene: FAM111A.
BabyScreen+ newborn screening v0.1947 FAM111A Zornitza Stark gene: FAM111A was added
gene: FAM111A was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: FAM111A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FAM111A were set to Kenny-Caffey syndrome, type 2, MIM# 127000
Review for gene: FAM111A was set to GREEN
Added comment: Condition is characterised by impaired skeletal development with small and dense bones, short stature, ocular abnormalities, and primary hypoparathyroidism with hypocalcemia. At least 10 unrelated cases reported with de novo missense variants. Intellectual disability/developmental delay is a rare feature of the condition.

Treatment: magnesium, calcium and calcitriol or alfacalcidol

Non-genetic confirmatory testing: serum calcium, parathyroid hormone level, calcitonin level
Sources: Expert Review
BabyScreen+ newborn screening v0.1946 ERCC6L2 Zornitza Stark Marked gene: ERCC6L2 as ready
BabyScreen+ newborn screening v0.1946 ERCC6L2 Zornitza Stark Gene: ercc6l2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1946 ERCC6L2 Zornitza Stark Classified gene: ERCC6L2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1946 ERCC6L2 Zornitza Stark Gene: ercc6l2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1945 ERCC6L2 Zornitza Stark gene: ERCC6L2 was added
gene: ERCC6L2 was added to Baby Screen+ newborn screening. Sources: Expert Review
treatable, haematological tags were added to gene: ERCC6L2.
Mode of inheritance for gene: ERCC6L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC6L2 were set to 24507776; 27185855
Phenotypes for gene: ERCC6L2 were set to Bone marrow failure syndrome 2, MIM# 615715
Review for gene: ERCC6L2 was set to AMBER
Added comment: Trilineage bone marrow failure, learning disabilities, and microcephaly. Three consanguineous families reported, but two with the same truncating variant, founder effect likely.

Treatment: bone marrow transplant.

Amber rating due to limited number of families reported.
Sources: Expert Review
BabyScreen+ newborn screening v0.1944 DOCK2 Zornitza Stark Marked gene: DOCK2 as ready
BabyScreen+ newborn screening v0.1944 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1944 DOCK2 Zornitza Stark Tag treatable tag was added to gene: DOCK2.
Tag immunological tag was added to gene: DOCK2.
BabyScreen+ newborn screening v0.1944 DOCK2 Zornitza Stark Classified gene: DOCK2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1944 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1943 DOCK2 Zornitza Stark gene: DOCK2 was added
gene: DOCK2 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: DOCK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOCK2 were set to 26083206; 29204803; 33928462; 30826364; 30838481; 11518968
Phenotypes for gene: DOCK2 were set to Immunodeficiency 40 MIM# 616433
Review for gene: DOCK2 was set to GREEN
Added comment: 13 unrelated individuals; two mouse models; 10 biallelic mutations found (6 led to premature termination of the protein & 4 missense mutations affecting conserved residues) All patients presented with combined immunodeficiency in infancy (defective IFN-mediated immunity), early onset of invasive bacterial and viral infections, functional defects in T/B/NK cells and elevated IgM (normal IgG/IgA).

Treatment: bone marrow transplant.

Non-genetic confirmatory testing: T and B Lymphocyte and Natural Killer Cell Profile
Sources: Expert Review
BabyScreen+ newborn screening v0.1942 DNASE2 Zornitza Stark Marked gene: DNASE2 as ready
BabyScreen+ newborn screening v0.1942 DNASE2 Zornitza Stark Gene: dnase2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1942 DNASE2 Zornitza Stark Classified gene: DNASE2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1942 DNASE2 Zornitza Stark Gene: dnase2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1941 DNASE2 Zornitza Stark Tag treatable tag was added to gene: DNASE2.
Tag immunological tag was added to gene: DNASE2.
BabyScreen+ newborn screening v0.1941 DNASE2 Zornitza Stark gene: DNASE2 was added
gene: DNASE2 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: DNASE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNASE2 were set to 29259162; 31775019
Phenotypes for gene: DNASE2 were set to Autoinflammatory-pancytopenia syndrome, MIM# 619858
Review for gene: DNASE2 was set to GREEN
Added comment: Inflammatory disorder characterized by splenomegaly, glomerulonephritis, liver fibrosis, circulating anti-DNA autoantibodies, and progressive arthritis. Three families and functional data.

Treatment: baricitinib

Non-genetic confirmatory testing: Interferon signature
Sources: Expert Review
BabyScreen+ newborn screening v0.1940 DNAJC21 Zornitza Stark Marked gene: DNAJC21 as ready
BabyScreen+ newborn screening v0.1940 DNAJC21 Zornitza Stark Gene: dnajc21 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1940 DNAJC21 Zornitza Stark Tag treatable tag was added to gene: DNAJC21.
Tag haematological tag was added to gene: DNAJC21.
BabyScreen+ newborn screening v0.1940 DNAJC21 Zornitza Stark Classified gene: DNAJC21 as Green List (high evidence)
BabyScreen+ newborn screening v0.1940 DNAJC21 Zornitza Stark Gene: dnajc21 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1939 DNAJC21 Zornitza Stark gene: DNAJC21 was added
gene: DNAJC21 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: DNAJC21 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC21 were set to 29700810; 28062395; 27346687
Phenotypes for gene: DNAJC21 were set to Bone marrow failure syndrome 3, MIM# 617052
Review for gene: DNAJC21 was set to GREEN
Added comment: Onset of pancytopenia in early childhood; variable nonspecific somatic abnormalities, including poor growth, microcephaly, and skin anomalies.

Treatment: oral pancreatic enzymes, fat-soluble vitamins, blood and/or platelet transfusions, granulocyte-colony stimulation factor, bone marrow transplant

Confirmatory non-genetic testing: no; FBE as pancytopenia evolves.
Sources: Expert Review
BabyScreen+ newborn screening v0.1938 CYP2R1 Zornitza Stark Marked gene: CYP2R1 as ready
BabyScreen+ newborn screening v0.1938 CYP2R1 Zornitza Stark Gene: cyp2r1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1938 CYP2R1 Zornitza Stark Tag treatable tag was added to gene: CYP2R1.
Tag endocrine tag was added to gene: CYP2R1.
BabyScreen+ newborn screening v0.1938 CYP2R1 Zornitza Stark Classified gene: CYP2R1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1938 CYP2R1 Zornitza Stark Gene: cyp2r1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1937 CYP2R1 Zornitza Stark gene: CYP2R1 was added
gene: CYP2R1 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: CYP2R1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP2R1 were set to 15128933; 28548312
Phenotypes for gene: CYP2R1 were set to Rickets due to defect in vitamin D 25-hydroxylation deficiency MIM#600081
Review for gene: CYP2R1 was set to GREEN
Added comment: At least 6 unrelated families reported.

Onset is generally in infancy.

Good response to vitamin D (calcifediol (25_OH_D3).

Confirmatory non-genetic testing: serum calcium, parathyroid hormone, 25-hydroxy vitamin D levels
Sources: Expert Review
BabyScreen+ newborn screening v0.1936 C17orf62 Zornitza Stark Marked gene: C17orf62 as ready
BabyScreen+ newborn screening v0.1936 C17orf62 Zornitza Stark Gene: c17orf62 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1936 C17orf62 Zornitza Stark Classified gene: C17orf62 as Green List (high evidence)
BabyScreen+ newborn screening v0.1936 C17orf62 Zornitza Stark Gene: c17orf62 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1935 C17orf62 Zornitza Stark gene: C17orf62 was added
gene: C17orf62 was added to Baby Screen+ newborn screening. Sources: Expert Review
new gene name, treatable, immunological tags were added to gene: C17orf62.
Mode of inheritance for gene: C17orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf62 were set to 30361506; 30312704; 28351984
Phenotypes for gene: C17orf62 were set to Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Review for gene: C17orf62 was set to GREEN
Added comment: Seven Icelandic families reported with same homozygous variant, p.Tyr2Ter and an additional family from different ethnic background with different homozygous splice site variant. Functional data, including mouse model. Gene also known as EROS and CYBC1 (HGNC approved name)

Primary immunodeficiency characterized by onset of recurrent infections and severe colitis in the first decade of life. Patients often present with features of inflammatory bowel disease and may show granulomata on biopsy. Patients are particularly susceptible to catalase-positive organisms, including Burkholderia cepacia, Legionella, and Candida albicans. Some patients may develop autoinflammatory symptoms, including recurrent fever in the absence of infection, hemolytic anemia, and lymphopenia. Additional features may include short stature, viral infections, cutaneous abscesses, pulmonary infections, and lymphadenitis. Haematopoietic bone marrow transplant is curative.

Non-genetic confirmatory assay: dihydrorhodamine assay
Sources: Expert Review
BabyScreen+ newborn screening v0.1934 CYB561 Zornitza Stark Marked gene: CYB561 as ready
BabyScreen+ newborn screening v0.1934 CYB561 Zornitza Stark Gene: cyb561 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1934 CYB561 Zornitza Stark Classified gene: CYB561 as Green List (high evidence)
BabyScreen+ newborn screening v0.1934 CYB561 Zornitza Stark Gene: cyb561 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1933 CYB561 Zornitza Stark Tag treatable tag was added to gene: CYB561.
Tag endocrine tag was added to gene: CYB561.
BabyScreen+ newborn screening v0.1933 CYB561 Zornitza Stark gene: CYB561 was added
gene: CYB561 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CYB561 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYB561 were set to 29343526; 31822578
Phenotypes for gene: CYB561 were set to Orthostatic hypotension 2, MIM# 618182
Review for gene: CYB561 was set to GREEN
Added comment: Three families reported.

Severe orthostatic hypotension, recurrent hypoglycemia, and low norepinephrine levels. The disorder has onset in infancy or early childhood.

Treatment: L-threo-3,4-dihydroxyphenylserine (droxidopa)

Non-genetic confirmatory testing: plasma norepinephrine, epinephrine, dopamine
Sources: Expert list
BabyScreen+ newborn screening v0.1932 Zornitza Stark Panel name changed from gNBS to Baby Screen+ newborn screening
Panel status changed from internal to public
BabyScreen+ newborn screening v0.1931 CR2 Zornitza Stark Marked gene: CR2 as ready
BabyScreen+ newborn screening v0.1931 CR2 Zornitza Stark Gene: cr2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1931 CR2 Zornitza Stark Phenotypes for gene: CR2 were changed from Hypogammaglobulinaemia to Immunodeficiency, common variable, 7, MIM# 614699
BabyScreen+ newborn screening v0.1930 CR2 Zornitza Stark Tag treatable tag was added to gene: CR2.
Tag immunological tag was added to gene: CR2.
BabyScreen+ newborn screening v0.1930 CR2 Zornitza Stark reviewed gene: CR2: Rating: RED; Mode of pathogenicity: None; Publications: 22035880, 26325596; Phenotypes: Immunodeficiency, common variable, 7, MIM# 614699; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1930 CORO1A Zornitza Stark Marked gene: CORO1A as ready
BabyScreen+ newborn screening v0.1930 CORO1A Zornitza Stark Gene: coro1a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1930 CORO1A Zornitza Stark Classified gene: CORO1A as Green List (high evidence)
BabyScreen+ newborn screening v0.1930 CORO1A Zornitza Stark Gene: coro1a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1929 CORO1A Zornitza Stark gene: CORO1A was added
gene: CORO1A was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CORO1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CORO1A were set to Immunodeficiency 8 MIM# 615401
Review for gene: CORO1A was set to GREEN
Added comment: 3 unrelated families and 1 unrelated individual reported with bi-allelic (deletion, missense, insertion) variants, resulting in premature stop codons and truncated protein/ alter a highly conserved residue in binding domain; one mouse model

All patients displayed T−B+NK+ SCID or CID presenting in early-onset recurrent infections and additional features that included EBV-associated lymphoproliferative disease and low immunoglobulin levels.

Congenital onset.

Treatment: bone marrow transplant

Non-genetic confirmatory testing: T and B Lymphocyte and Natural Killer Cell Profile
Sources: Expert list
BabyScreen+ newborn screening v0.1928 CDCA7 Zornitza Stark Marked gene: CDCA7 as ready
BabyScreen+ newborn screening v0.1928 CDCA7 Zornitza Stark Gene: cdca7 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1928 CDCA7 Zornitza Stark Classified gene: CDCA7 as Green List (high evidence)
BabyScreen+ newborn screening v0.1928 CDCA7 Zornitza Stark Gene: cdca7 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1927 CDCA7 Zornitza Stark Tag treatable tag was added to gene: CDCA7.
Tag immunological tag was added to gene: CDCA7.
BabyScreen+ newborn screening v0.1927 CDCA7 Zornitza Stark gene: CDCA7 was added
gene: CDCA7 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CDCA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDCA7 were set to 26216346
Phenotypes for gene: CDCA7 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 3, MIM# 616910
Review for gene: CDCA7 was set to GREEN
Added comment: Congenital onset, severe disorder. At least 4 unrelated families reported.

Treatment: replacement immunoglobulins, bone marrow transplant

Non-genetic confirmatory testing: immunoglobulin levels, cytogenetic analysis for centromeric instability, DNA methylation studies
Sources: Expert Review
BabyScreen+ newborn screening v0.1926 CD81 Zornitza Stark Marked gene: CD81 as ready
BabyScreen+ newborn screening v0.1926 CD81 Zornitza Stark Gene: cd81 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1926 CD81 Zornitza Stark Tag treatable tag was added to gene: CD81.
Tag immunological tag was added to gene: CD81.
BabyScreen+ newborn screening v0.1926 CD81 Zornitza Stark gene: CD81 was added
gene: CD81 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CD81 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD81 were set to 20237408
Phenotypes for gene: CD81 were set to Immunodeficiency, common variable, 6, MIM# 613496
Review for gene: CD81 was set to RED
Added comment: CVID, which would be congenital, severe and treatable with replacement immunoglobulins.

However, only a single individual reported.
Sources: Expert Review
BabyScreen+ newborn screening v0.1925 CD70 Zornitza Stark Marked gene: CD70 as ready
BabyScreen+ newborn screening v0.1925 CD70 Zornitza Stark Gene: cd70 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1925 CD70 Zornitza Stark Classified gene: CD70 as Green List (high evidence)
BabyScreen+ newborn screening v0.1925 CD70 Zornitza Stark Gene: cd70 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1924 CD70 Zornitza Stark gene: CD70 was added
gene: CD70 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CD70 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CD70 were set to Lymphoproliferative syndrome 3, MIM# 618261
Review for gene: CD70 was set to GREEN
Added comment: Severe lymphoproliferation following EBV infection.

Treatment: bone marrow transplant.

Non-genetic confirmatory testing: immunoglobulin levels, T and B Lymphocyte and Natural Killer Cell Profile
Sources: Expert Review
BabyScreen+ newborn screening v0.1923 CD55 Zornitza Stark Marked gene: CD55 as ready
BabyScreen+ newborn screening v0.1923 CD55 Zornitza Stark Gene: cd55 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1923 CD55 Zornitza Stark Classified gene: CD55 as Green List (high evidence)
BabyScreen+ newborn screening v0.1923 CD55 Zornitza Stark Gene: cd55 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1922 CD55 Zornitza Stark Tag treatable tag was added to gene: CD55.
Tag immunological tag was added to gene: CD55.
BabyScreen+ newborn screening v0.1922 CD55 Zornitza Stark gene: CD55 was added
gene: CD55 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CD55 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD55 were set to 33398182
Phenotypes for gene: CD55 were set to Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy, MIM# 226300
Review for gene: CD55 was set to GREEN
Added comment: Severe congenital disorder, high mortality.

Treatment: Eculizumab

Non-genetic confirmatory testing: albumin level, immunoglobulin level
Sources: Expert Review
BabyScreen+ newborn screening v0.1921 CD40 Zornitza Stark Marked gene: CD40 as ready
BabyScreen+ newborn screening v0.1921 CD40 Zornitza Stark Gene: cd40 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1921 CD40 Zornitza Stark Marked gene: CD40 as ready
BabyScreen+ newborn screening v0.1921 CD40 Zornitza Stark Gene: cd40 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1921 CD40 Zornitza Stark Classified gene: CD40 as Green List (high evidence)
BabyScreen+ newborn screening v0.1921 CD40 Zornitza Stark Gene: cd40 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1920 CD40 Zornitza Stark gene: CD40 was added
gene: CD40 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CD40 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD40 were set to 29884852
Phenotypes for gene: CD40 were set to Immunodeficiency with hyper-IgM, type 3, MIM# 606843
Review for gene: CD40 was set to GREEN
Added comment: Severity can be variable but generally congenital onset, and predisposition to severe infections. Note CD40L already included.

Treatment: bone marrow transplantation.

Non-genetic confirmatory testing: immunoglobulin levels, flow cytometric analysis
Sources: Expert list
BabyScreen+ newborn screening v0.1919 CD3G Zornitza Stark Marked gene: CD3G as ready
BabyScreen+ newborn screening v0.1919 CD3G Zornitza Stark Gene: cd3g has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1919 CD3G Zornitza Stark Classified gene: CD3G as Green List (high evidence)
BabyScreen+ newborn screening v0.1919 CD3G Zornitza Stark Gene: cd3g has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1918 CD3G Zornitza Stark edited their review of gene: CD3G: Changed rating: GREEN
BabyScreen+ newborn screening v0.1918 CD3G Zornitza Stark Tag treatable tag was added to gene: CD3G.
Tag immunological tag was added to gene: CD3G.
BabyScreen+ newborn screening v0.1918 CD3G Zornitza Stark gene: CD3G was added
gene: CD3G was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CD3G was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD3G were set to 31921117
Phenotypes for gene: CD3G were set to Immunodeficiency 17; CD3 gamma deficient MIM# 615607
Added comment: 10 affected individuals from 5 unrelated families; homozygous and compound heterozygous variants (splicing, missense and small deletion variants) identified resulting in premature stop codons and truncated protein; multiple mouse models.

All individuals displayed immune deficiency and autoimmunity of variable severity. Some individuals presented at birth with failure to thrive due to lethal SCID features. The most common immunologic profile includes partial T lymphocytopenia and low CD3, with normal B cells, NK cells, and immunoglobulins.

Congenital onset.

Treatment: replacement immunoglobulin

Non-genetic confirmatory testing: immunoglobulin levels
Sources: Expert list
BabyScreen+ newborn screening v0.1917 CD27 Zornitza Stark Marked gene: CD27 as ready
BabyScreen+ newborn screening v0.1917 CD27 Zornitza Stark Gene: cd27 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1917 CD27 Zornitza Stark Classified gene: CD27 as Green List (high evidence)
BabyScreen+ newborn screening v0.1917 CD27 Zornitza Stark Gene: cd27 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1916 CD27 Zornitza Stark Tag treatable tag was added to gene: CD27.
Tag immunological tag was added to gene: CD27.
BabyScreen+ newborn screening v0.1916 CD27 Zornitza Stark gene: CD27 was added
gene: CD27 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CD27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD27 were set to 22197273; 22801960; 22365582; 25843314; 11062504
Phenotypes for gene: CD27 were set to CD27-deficiency MIM# 615122
Review for gene: CD27 was set to GREEN
Added comment: 17 affected individuals from 9 unrelated families; homozygous (missense) and compound heterozygous (missense/ nonsense) variants identified in CD27; one mouse model. Affected individuals present with varied phenotypes (even within the same families); most commonly with lymphadenopathy, fever, hepatosplenomegaly, EBV-related infections, and immunodeficiency associated with hypogammaglobulinaemia. However, some CD27-deficient individuals are asymptomatic or display borderline-low hypogammaglobulinaemia.

Treatment: replacement immunoglobulin treatment, rituximab, Bone marrow transplant.

Non-genetic confirmatory testing: immunoglobulin levels
Sources: Expert list
BabyScreen+ newborn screening v0.1915 CD247 Zornitza Stark Marked gene: CD247 as ready
BabyScreen+ newborn screening v0.1915 CD247 Zornitza Stark Gene: cd247 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1915 CD247 Zornitza Stark Classified gene: CD247 as Green List (high evidence)
BabyScreen+ newborn screening v0.1915 CD247 Zornitza Stark Gene: cd247 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1914 CD247 Zornitza Stark Tag treatable tag was added to gene: CD247.
Tag immunological tag was added to gene: CD247.
BabyScreen+ newborn screening v0.1914 CD247 Zornitza Stark gene: CD247 was added
gene: CD247 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CD247 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD247 were set to 16672702; 17170122
Phenotypes for gene: CD247 were set to Immunodeficiency 25, MIM# 610163
Review for gene: CD247 was set to GREEN
Added comment: Two reports in the literature, note additional two reports in ClinVar; functional data.

Congenital onset. Absent T cells, resulting in severe immunodeficiency.

Treatment: bone marrow transplant.

Non-genetic confirmatory testing: T, B and NK cell counts
Sources: Expert Review
BabyScreen+ newborn screening v0.1913 CD19 Zornitza Stark Marked gene: CD19 as ready
BabyScreen+ newborn screening v0.1913 CD19 Zornitza Stark Gene: cd19 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1913 CD19 Zornitza Stark Tag treatable tag was added to gene: CD19.
Tag immunological tag was added to gene: CD19.
BabyScreen+ newborn screening v0.1913 CD19 Zornitza Stark Classified gene: CD19 as Green List (high evidence)
BabyScreen+ newborn screening v0.1913 CD19 Zornitza Stark Gene: cd19 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1912 CD19 Zornitza Stark gene: CD19 was added
gene: CD19 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CD19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CD19 were set to Immunodeficiency, common variable, 3, MIM# 613493
Review for gene: CD19 was set to GREEN
Added comment: More than 5 unrelated families reported. Clinical features include increased susceptibility to infection, hypogammaglobulinaemia, and normal numbers of mature B cells in blood, indicating a B-cell antibody-deficient immunodeficiency disorder.

Onset is congenital.

Treatment: IVIG

Non-genetic confirmatory testing: immunoglobulin levels
Sources: Expert list
BabyScreen+ newborn screening v0.1911 CAV1 Zornitza Stark Marked gene: CAV1 as ready
BabyScreen+ newborn screening v0.1911 CAV1 Zornitza Stark Gene: cav1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1911 CAV1 Zornitza Stark Classified gene: CAV1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1911 CAV1 Zornitza Stark Gene: cav1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1910 CAV1 Zornitza Stark Tag treatable tag was added to gene: CAV1.
Tag metabolic tag was added to gene: CAV1.
BabyScreen+ newborn screening v0.1910 CAV1 Zornitza Stark gene: CAV1 was added
gene: CAV1 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CAV1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAV1 were set to 29704234
Phenotypes for gene: CAV1 were set to Lipodystrophy, congenital generalized, type 3, MIM# 612526
Review for gene: CAV1 was set to GREEN
Added comment: Established gene-disease association.

Bi-allelic disease is more severe. Onset is congenital.

Treatment: metreleptin

Non-genetic confirmatory testing: leptin levels
Sources: Expert list
BabyScreen+ newborn screening v0.1908 PRDX1 Zornitza Stark Marked gene: PRDX1 as ready
BabyScreen+ newborn screening v0.1908 PRDX1 Zornitza Stark Gene: prdx1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1908 PRDX1 Zornitza Stark Classified gene: PRDX1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1908 PRDX1 Zornitza Stark Gene: prdx1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1907 PRDX1 Zornitza Stark Tag for review tag was added to gene: PRDX1.
BabyScreen+ newborn screening v0.1907 PNP Zornitza Stark Marked gene: PNP as ready
BabyScreen+ newborn screening v0.1907 PNP Zornitza Stark Gene: pnp has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1907 PNP Zornitza Stark Tag treatable tag was added to gene: PNP.
Tag immunological tag was added to gene: PNP.
BabyScreen+ newborn screening v0.1907 PNP Zornitza Stark Classified gene: PNP as Green List (high evidence)
BabyScreen+ newborn screening v0.1907 PNP Zornitza Stark Gene: pnp has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1906 MTHFR Zornitza Stark Marked gene: MTHFR as ready
BabyScreen+ newborn screening v0.1906 MTHFR Zornitza Stark Gene: mthfr has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1906 MTHFR Zornitza Stark Phenotypes for gene: MTHFR were changed from Homocystinuria due to MTHFR deficiency to Homocystinuria due to MTHFR deficiency MIM#236250
BabyScreen+ newborn screening v0.1905 MTHFR Zornitza Stark Publications for gene: MTHFR were set to
BabyScreen+ newborn screening v0.1904 MTHFR Zornitza Stark Classified gene: MTHFR as Red List (low evidence)
BabyScreen+ newborn screening v0.1904 MTHFR Zornitza Stark Gene: mthfr has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1903 MCCC2 Zornitza Stark Marked gene: MCCC2 as ready
BabyScreen+ newborn screening v0.1903 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1903 MCCC2 Zornitza Stark Phenotypes for gene: MCCC2 were changed from 3-Methylcrotonyl-CoA carboxylase 2 deficiency; 3-Methylcrotonyl-CoA carboxylase 2 deficiency, MIM# 210210 to 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210
BabyScreen+ newborn screening v0.1902 MCCC2 Zornitza Stark Publications for gene: MCCC2 were set to
BabyScreen+ newborn screening v0.1901 MCCC2 Zornitza Stark reviewed gene: MCCC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1901 MCCC1 Zornitza Stark Marked gene: MCCC1 as ready
BabyScreen+ newborn screening v0.1901 MCCC1 Zornitza Stark Gene: mccc1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1901 MCCC1 Zornitza Stark Phenotypes for gene: MCCC1 were changed from 3-Methylcrotonyl-CoA carboxylase 1 deficiency; 3-Methylcrotonyl-CoA carboxylase 1 deficiency, MIM# 210200 to 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200
BabyScreen+ newborn screening v0.1900 MCCC1 Zornitza Stark Publications for gene: MCCC1 were set to
BabyScreen+ newborn screening v0.1899 MCCC1 Zornitza Stark Classified gene: MCCC1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1899 MCCC1 Zornitza Stark Gene: mccc1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1898 MCCC1 Zornitza Stark reviewed gene: MCCC1: Rating: RED; Mode of pathogenicity: None; Publications: 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1898 MAT1A Zornitza Stark Marked gene: MAT1A as ready
BabyScreen+ newborn screening v0.1898 MAT1A Zornitza Stark Gene: mat1a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1898 MAT1A Zornitza Stark Mode of inheritance for gene: MAT1A was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1897 MAT1A Zornitza Stark Phenotypes for gene: MAT1A were changed from Methionine adenosyltransferase deficiency to Methionine adenosyltransferase deficiency MIM#250850
BabyScreen+ newborn screening v0.1896 LIAS Zornitza Stark Marked gene: LIAS as ready
BabyScreen+ newborn screening v0.1896 LIAS Zornitza Stark Gene: lias has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1896 LIAS Zornitza Stark Publications for gene: LIAS were set to PMID: 24334290, 24777537,
BabyScreen+ newborn screening v0.1895 LIAS Zornitza Stark Source Expert list was removed from LIAS.
Source Expert Review was added to LIAS.
Rating Changed from No List (delete) to Red List (low evidence)
BabyScreen+ newborn screening v0.1894 LIAS Zornitza Stark All sources for gene: LIAS were removed
BabyScreen+ newborn screening v0.1893 LIAS Zornitza Stark All sources for gene: LIAS were removed
BabyScreen+ newborn screening v0.1892 LIAS Zornitza Stark Classified gene: LIAS as Red List (low evidence)
BabyScreen+ newborn screening v0.1892 LIAS Zornitza Stark Gene: lias has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1891 HPD Zornitza Stark Marked gene: HPD as ready
BabyScreen+ newborn screening v0.1891 HPD Zornitza Stark Gene: hpd has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1891 HPD Zornitza Stark Publications for gene: HPD were set to
BabyScreen+ newborn screening v0.1890 HPD Zornitza Stark reviewed gene: HPD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Tyrosinemia, type III MIM#276710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1890 HIBCH Zornitza Stark Tag for review tag was added to gene: HIBCH.
BabyScreen+ newborn screening v0.1890 HMGCS2 Zornitza Stark Marked gene: HMGCS2 as ready
BabyScreen+ newborn screening v0.1890 HMGCS2 Zornitza Stark Gene: hmgcs2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1890 HMGCS2 Zornitza Stark Classified gene: HMGCS2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1890 HMGCS2 Zornitza Stark Gene: hmgcs2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1889 HMGCS2 Zornitza Stark Tag for review tag was added to gene: HMGCS2.
Tag treatable tag was added to gene: HMGCS2.
Tag metabolic tag was added to gene: HMGCS2.
BabyScreen+ newborn screening v0.1889 HMGCS2 Zornitza Stark reviewed gene: HMGCS2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: HMG-CoA synthase-2 deficiency MIM#605911; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1889 HIBCH Zornitza Stark Marked gene: HIBCH as ready
BabyScreen+ newborn screening v0.1889 HIBCH Zornitza Stark Gene: hibch has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1889 HIBCH Zornitza Stark Phenotypes for gene: HIBCH were changed from Neurodegeneration, progressive infantile to 3-hydroxyisobutryl-CoA hydrolase deficiency MIM#250620
BabyScreen+ newborn screening v0.1888 HIBCH Zornitza Stark Publications for gene: HIBCH were set to
BabyScreen+ newborn screening v0.1887 HIBCH Zornitza Stark Tag treatable tag was added to gene: HIBCH.
Tag metabolic tag was added to gene: HIBCH.
BabyScreen+ newborn screening v0.1887 HIBCH Zornitza Stark Classified gene: HIBCH as Green List (high evidence)
BabyScreen+ newborn screening v0.1887 HIBCH Zornitza Stark Gene: hibch has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1886 GLIS3 Zornitza Stark Marked gene: GLIS3 as ready
BabyScreen+ newborn screening v0.1886 GLIS3 Zornitza Stark Gene: glis3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1886 GLIS3 Zornitza Stark Phenotypes for gene: GLIS3 were changed from Diabetes mellitus, neonatal, with congenital hypothyroidism; Diabetes mellitus, neonatal, with congenital hypothyroidism, MIM# 610199 to Diabetes mellitus, neonatal, with congenital hypothyroidism MIM#610199
BabyScreen+ newborn screening v0.1885 GLIS3 Zornitza Stark Publications for gene: GLIS3 were set to
BabyScreen+ newborn screening v0.1884 GLIS3 Zornitza Stark Classified gene: GLIS3 as Green List (high evidence)
BabyScreen+ newborn screening v0.1884 GLIS3 Zornitza Stark Gene: glis3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1883 GLIS3 Zornitza Stark Tag treatable tag was added to gene: GLIS3.
Tag endocrine tag was added to gene: GLIS3.
BabyScreen+ newborn screening v0.1883 GLIS3 Zornitza Stark reviewed gene: GLIS3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diabetes mellitus, neonatal, with congenital hypothyroidism MIM#610199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1883 PRDX1 Lilian Downie gene: PRDX1 was added
gene: PRDX1 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: PRDX1 was set to Other
Publications for gene: PRDX1 were set to PMID: 20301503, PMID: 29396438, PMID: 34215320, PMID: 33982424
Phenotypes for gene: PRDX1 were set to Methylmalonic aciduria and homocystinuria, cblC type, digenic MIM#277400
Review for gene: PRDX1 was set to GREEN
Added comment: Digenic inheritance with mutation in other allele of MMACHC
On GUARDIAN and Rx genes list

Recently, three individuals who are double heterozygous for pathogenic variants in MMACHC and PRDX1 have been identified. PRDX1 is a neighboring gene on chromosome 1 transcribed from the reverse strand. Variants identified in PRDX1 located at the intron 5 splice acceptor site caused skipping of exon 6, transcription of antisense MMACHC, and hypermethylation of the MMACHC promoter/exon 1, resulting in no gene expression from that allele [Guéant et al 2018].

Treatable with cobalamin, carnitine & diet. NB MMACHC is green on our list, on newborn screening.
Sources: Expert list
BabyScreen+ newborn screening v0.1883 PNP Lilian Downie gene: PNP was added
gene: PNP was added to gNBS. Sources: Expert list
Mode of inheritance for gene: PNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNP were set to PMID: 35968787, PMID: 35063692, PMID: 30885031, PMID: 1931007, PMID: 28674683
Phenotypes for gene: PNP were set to Immunodeficiency due to purine nucleoside phosphorylase deficiency MIM#613179
Review for gene: PNP was set to GREEN
Added comment: Decreased T cell function - SCID immunodeficiency
variable neurological phenotype
childhood onset
Treat bone marrow transplant
Sources: Expert list
BabyScreen+ newborn screening v0.1883 MTHFR Lilian Downie reviewed gene: MTHFR: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34214447; Phenotypes: Homocystinuria due to MTHFR deficiency MIM#236250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1883 MCCC2 Lilian Downie reviewed gene: MCCC2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 22642865; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1883 GATM Zornitza Stark Tag treatable tag was added to gene: GATM.
Tag metabolic tag was added to gene: GATM.
BabyScreen+ newborn screening v0.1883 GATM Zornitza Stark Marked gene: GATM as ready
BabyScreen+ newborn screening v0.1883 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1883 GATM Zornitza Stark Classified gene: GATM as Green List (high evidence)
BabyScreen+ newborn screening v0.1883 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1882 GATM Zornitza Stark reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301745; Phenotypes: Cerebral creatine deficiency syndrome 3, MIM#612718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1882 FOXE1 Zornitza Stark Marked gene: FOXE1 as ready
BabyScreen+ newborn screening v0.1882 FOXE1 Zornitza Stark Gene: foxe1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1882 FOXE1 Zornitza Stark Phenotypes for gene: FOXE1 were changed from Bamforth-Lazarus syndrome to Bamforth-Lazarus syndrome MIM# 241850
BabyScreen+ newborn screening v0.1881 FOXE1 Zornitza Stark Publications for gene: FOXE1 were set to
BabyScreen+ newborn screening v0.1880 FOXE1 Zornitza Stark Classified gene: FOXE1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1880 FOXE1 Zornitza Stark Gene: foxe1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1879 FOXE1 Zornitza Stark Tag treatable tag was added to gene: FOXE1.
Tag endocrine tag was added to gene: FOXE1.
Tag deafness tag was added to gene: FOXE1.
BabyScreen+ newborn screening v0.1879 ALDH4A1 Zornitza Stark Marked gene: ALDH4A1 as ready
BabyScreen+ newborn screening v0.1879 ALDH4A1 Zornitza Stark Gene: aldh4a1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1879 ALDH4A1 Zornitza Stark Phenotypes for gene: ALDH4A1 were changed from Hyperprolinemia, type II to Hyperprolinemia, type II MIM#239510
BabyScreen+ newborn screening v0.1878 ALDH4A1 Zornitza Stark Publications for gene: ALDH4A1 were set to
BabyScreen+ newborn screening v0.1877 ALDH4A1 Zornitza Stark Classified gene: ALDH4A1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1877 ALDH4A1 Zornitza Stark Gene: aldh4a1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1876 ALDH4A1 Zornitza Stark Tag treatable tag was added to gene: ALDH4A1.
Tag metabolic tag was added to gene: ALDH4A1.
BabyScreen+ newborn screening v0.1876 ALDH4A1 Zornitza Stark reviewed gene: ALDH4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperprolinemia, type II MIM#239510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1876 ACADSB Zornitza Stark Marked gene: ACADSB as ready
BabyScreen+ newborn screening v0.1876 ACADSB Zornitza Stark Gene: acadsb has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1876 ACADSB Zornitza Stark Phenotypes for gene: ACADSB were changed from 2-Methylbutyryl-CoA dehydrogenase deficiency to 2-methylbutyrylglycinuria MIM#610006
BabyScreen+ newborn screening v0.1875 ACADS Zornitza Stark Marked gene: ACADS as ready
BabyScreen+ newborn screening v0.1875 ACADS Zornitza Stark Gene: acads has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1875 ABCD4 Zornitza Stark Marked gene: ABCD4 as ready
BabyScreen+ newborn screening v0.1875 ABCD4 Zornitza Stark Gene: abcd4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1875 ABCD4 Zornitza Stark Phenotypes for gene: ABCD4 were changed from MAHCJ, MIM#614857; Methylmalonic aciduria and homocystinuria, cblJ TYPE; Methylmalonic aciduria and homocystinuria, cblJ type to Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857
BabyScreen+ newborn screening v0.1874 ABCD4 Zornitza Stark Publications for gene: ABCD4 were set to
BabyScreen+ newborn screening v0.1873 ABCD4 Zornitza Stark Classified gene: ABCD4 as Green List (high evidence)
BabyScreen+ newborn screening v0.1873 ABCD4 Zornitza Stark Gene: abcd4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1872 ABCD4 Zornitza Stark reviewed gene: ABCD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22922874, 30651581, 28572511, 31113616; Phenotypes: Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 MCCC1 Lilian Downie reviewed gene: MCCC1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 22642865; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 MAT1A Lilian Downie reviewed gene: MAT1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Methionine adenosyltransferase deficiency MIM#250850; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 LIAS Lilian Downie gene: LIAS was added
gene: LIAS was added to gNBS. Sources: Expert list
Mode of inheritance for gene: LIAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIAS were set to PMID: 24334290, 24777537,
Phenotypes for gene: LIAS were set to Hyperglycinemia, lactic acidosis, and seizures MIM#614462
Review for gene: LIAS was set to RED
Added comment: pyruvate dehydrogenase lipoic acid synthetase deficiency (PDHLD)
increased serum glycine and lactate in the first days of life, hypotonia, seizures, early death
No treatment
Sources: Expert list
BabyScreen+ newborn screening v0.1872 HPD Lilian Downie reviewed gene: HPD: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 9343288, PMID: 11916315, PMID: 32520295; Phenotypes: Tyrosinemia, type III MIM#276710; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 HMGCS2 Lilian Downie gene: HMGCS2 was added
gene: HMGCS2 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: HMGCS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMGCS2 were set to PMID: 32259399, 32470406
Phenotypes for gene: HMGCS2 were set to HMG-CoA synthase-2 deficiency MIM#605911
Penetrance for gene: HMGCS2 were set to Incomplete
Review for gene: HMGCS2 was set to AMBER
Added comment: Metabolic disorder; patients present with hypoketotic hypoglycemia, encephalopathy, and hepatomegaly, usually precipitated by an intercurrent infection or prolonged fasting. Recover completely between illnesses, do develop fatty liver.
?incomplete penetrance or variable age of onset
On GUARDIAN and Rx Genes
Rx IV glucose during acute episodes, avoid prolonged fasting
Metabolic parameters are normal in between episodes, so no ability to do a confirmatory biochemical test.
Pros: readily treatable if child has an episode Cons: unncessary worry as child may never have episode
Super rare ?30 cases
Discuss with JC?
Sources: Expert list
BabyScreen+ newborn screening v0.1872 HIBCH Lilian Downie reviewed gene: HIBCH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32642440, PMID: 17160907, PMID: 27400804; Phenotypes: 3-hydroxyisobutryl-CoA hydrolase deficiency MIM#250620; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 GLIS3 Lilian Downie reviewed gene: GLIS3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29406006, 29992946, 27899417, PMID: 26259131; Phenotypes: Diabetes mellitus, neonatal, with congenital hypothyroidism MIM#610199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 GATM Lilian Downie gene: GATM was added
gene: GATM was added to gNBS. Sources: Expert list
Mode of inheritance for gene: GATM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GATM were set to PMID: 20301745, 34972654
Phenotypes for gene: GATM were set to Cerebral creatine deficiency syndrome 3 MIM#612718
Review for gene: GATM was set to GREEN
Added comment: GUARDIAN gene list (not on babyseq or rxgenes)
ID and myopathy, early onset
Rx creatine
Seems like a good fit? I'm not clear from the literature how effective the treatment is. check with JC
Sources: Expert list
BabyScreen+ newborn screening v0.1872 FOXE1 Lilian Downie reviewed gene: FOXE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33272083, 2918525, 20453517, 35963604; Phenotypes: Bamforth-Lazarus syndrome MIM# 241850; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 ALDH4A1 Lilian Downie reviewed gene: ALDH4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31884946, 34037900, 30930802, 34302426; Phenotypes: Hyperprolinemia, type II MIM#239510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 ACADSB Lilian Downie reviewed gene: ACADSB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 2-methylbutyrylglycinuria MIM#610006; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 ACADS Lilian Downie reviewed gene: ACADS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Acyl-CoA dehydrogenase, short-chain, deficiency of MIM#201470; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 ABCD4 Lilian Downie reviewed gene: ABCD4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22922874, PMID: 33729671; Phenotypes: Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1872 TANGO2 Zornitza Stark Marked gene: TANGO2 as ready
BabyScreen+ newborn screening v0.1872 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1872 TANGO2 Zornitza Stark Phenotypes for gene: TANGO2 were changed from Cardiomyopathy; Metabolic Crises; Arrhythmia; Neurodevelopmental to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878
BabyScreen+ newborn screening v0.1871 TANGO2 Zornitza Stark Classified gene: TANGO2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1871 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1870 TANGO2 Zornitza Stark Tag treatable tag was added to gene: TANGO2.
Tag metabolic tag was added to gene: TANGO2.
BabyScreen+ newborn screening v0.1870 LAMP2 Zornitza Stark Phenotypes for gene: LAMP2 were changed from Danon disease, MIM# 300257 to Danon disease, MIM# 300257
BabyScreen+ newborn screening v0.1869 LAMP2 Zornitza Stark Classified gene: LAMP2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1869 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1868 NKX2-5 Zornitza Stark Marked gene: NKX2-5 as ready
BabyScreen+ newborn screening v0.1868 NKX2-5 Zornitza Stark Gene: nkx2-5 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1868 NKX2-5 Zornitza Stark Phenotypes for gene: NKX2-5 were changed from Congenital heart disease to Atrial septal defect 7, with or without AV conduction defects, MIM# 108900
BabyScreen+ newborn screening v0.1867 NKX2-5 Zornitza Stark Tag cardiac tag was added to gene: NKX2-5.
BabyScreen+ newborn screening v0.1867 NKX2-5 Zornitza Stark Classified gene: NKX2-5 as Green List (high evidence)
BabyScreen+ newborn screening v0.1867 NKX2-5 Zornitza Stark Gene: nkx2-5 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1866 ACTA2 Zornitza Stark Mode of inheritance for gene: ACTA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1865 HADHA Ari Horton reviewed gene: HADHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31575911; Phenotypes: Cardiomyopathy, Metabolic Disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1865 TANGO2 Ari Horton changed review comment from: Folate may assist with TANGO2
DOI: https://doi.org/10.21203/rs.3.rs-1778084/v1

While chronic symptoms are predominantly neurodevelopmental, metabolic stressors such as fasting, dehydration, illness, and excessive heat can trigger episodic metabolic crises characterized by encephalopathy, ataxia, muscle weakness, rhabdomyolysis, and hypoglycemia. During these events, patients can develop acute life-threatening cardiac arrhythmias. Arrhythmias typically initiate with isolated premature ventricular contractions (PVC) followed by recalcitrant ventricular tachycardia. Because these lethal arrhythmias usually do not respond to standard antiarrhythmic therapies, cardiac arrhythmias are the leading cause of death in TDD

Fasting and feeding recommendations to reduce crises and improve cardiac status and neurodev outcomes, reduce risk of cardiac arrhythmias and SCDY

Natural history study (ClinicalTrials.gov Identifier: NCT05374616) strongly suggests that subjects on a multivitamin or a Bcomplex vitamin supplement have a greatly reduced risk for metabolic crises and cardiac arrhythmias

Specific diet and fasting plans are recommended for all patients from the neonatal period
Sources: Expert Review; to: Folate may assist with TANGO2
DOI: https://doi.org/10.21203/rs.3.rs-1778084/v1

PMID: 35568137

While chronic symptoms are predominantly neurodevelopmental, metabolic stressors such as fasting, dehydration, illness, and excessive heat can trigger episodic metabolic crises characterized by encephalopathy, ataxia, muscle weakness, rhabdomyolysis, and hypoglycemia. During these events, patients can develop acute life-threatening cardiac arrhythmias. Arrhythmias typically initiate with isolated premature ventricular contractions (PVC) followed by recalcitrant ventricular tachycardia. Because these lethal arrhythmias usually do not respond to standard antiarrhythmic therapies, cardiac arrhythmias are the leading cause of death in TDD

Fasting and feeding recommendations to reduce crises and improve cardiac status and neurodev outcomes, reduce risk of cardiac arrhythmias and SCDY

Natural history study (ClinicalTrials.gov Identifier: NCT05374616) strongly suggests that subjects on a multivitamin or a Bcomplex vitamin supplement have a greatly reduced risk for metabolic crises and cardiac arrhythmias

Twenty-seven children were admitted for 43 cardiac crises (median age 6.4 years; interquartile range [IQR] 2.4–9.8 years) at 14 centers. During crisis, QTc prolongation occurred in all (median 547 ms; IQR 504–600 ms) and a type I Brugada pattern in 8 (26%). Arrhythmias included VT in 21 (78%), supraventricular tachycardia in 3 (11%), and heart block in 1 (4%). Nineteen patients (70%) developed cardiomyopathy, and 20 (74%) experienced a cardiac arrest. There were 10 deaths (37%), 6 related to arrhythmias. In 5 patients, recalcitrant VT occurred despite use of antiarrhythmic drugs. In 6 patients, arrhythmias were controlled after extracorporeal membrane oxygenation (ECMO) support; 5 of these patients survived. Among 10 patients who survived VT without ECMO, successful treatment included intravenous magnesium, isoproterenol, and atrial pacing in multiple cases and verapamil in 1 patient. Initiation of feeds seemed to decrease VT events.

Specific diet and fasting plans are recommended for all patients from the neonatal period
Sources: Expert Review
BabyScreen+ newborn screening v0.1865 TANGO2 Ari Horton gene: TANGO2 was added
gene: TANGO2 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TANGO2 were set to Cardiomyopathy; Metabolic Crises; Arrhythmia; Neurodevelopmental
Penetrance for gene: TANGO2 were set to Complete
Review for gene: TANGO2 was set to GREEN
Added comment: Folate may assist with TANGO2
DOI: https://doi.org/10.21203/rs.3.rs-1778084/v1

While chronic symptoms are predominantly neurodevelopmental, metabolic stressors such as fasting, dehydration, illness, and excessive heat can trigger episodic metabolic crises characterized by encephalopathy, ataxia, muscle weakness, rhabdomyolysis, and hypoglycemia. During these events, patients can develop acute life-threatening cardiac arrhythmias. Arrhythmias typically initiate with isolated premature ventricular contractions (PVC) followed by recalcitrant ventricular tachycardia. Because these lethal arrhythmias usually do not respond to standard antiarrhythmic therapies, cardiac arrhythmias are the leading cause of death in TDD

Fasting and feeding recommendations to reduce crises and improve cardiac status and neurodev outcomes, reduce risk of cardiac arrhythmias and SCDY

Natural history study (ClinicalTrials.gov Identifier: NCT05374616) strongly suggests that subjects on a multivitamin or a Bcomplex vitamin supplement have a greatly reduced risk for metabolic crises and cardiac arrhythmias

Specific diet and fasting plans are recommended for all patients from the neonatal period
Sources: Expert Review
BabyScreen+ newborn screening v0.1865 LAMP2 Ari Horton reviewed gene: LAMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Childhood onset cardiomyopathy (Severe), Neuordevelopmental phenotype; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.1865 NKX2-5 Ari Horton reviewed gene: NKX2-5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neonatal onset cardiomyopathy, Congenital Heart Disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
BabyScreen+ newborn screening v0.1865 GATA4 Ari Horton reviewed gene: GATA4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, Congenital Heart Disease, Arrhythmia, Extra-cardiac Manifestations; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
BabyScreen+ newborn screening v0.1865 ACTA2 Ari Horton reviewed gene: ACTA2: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1865 MCFD2 Zornitza Stark Classified gene: MCFD2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1865 MCFD2 Zornitza Stark Gene: mcfd2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1864 MCFD2 Zornitza Stark changed review comment from: Reviewed with Meg Wall, haematologist.
Treatable, including with prophylactic DDAVP, include.; to: Reviewed with Meg Wall, haematologist.
Treatable, including with prophylactic DDAVP; however, generally mild, therefore exclude.
BabyScreen+ newborn screening v0.1864 MCFD2 Zornitza Stark edited their review of gene: MCFD2: Changed rating: AMBER
BabyScreen+ newborn screening v0.1864 HBB Zornitza Stark Phenotypes for gene: HBB were changed from Sickle cell anaemia, MIM# 603903; Thalassaemia, beta, MIM# 613985 to Sickle cell anaemia, MIM# 603903
BabyScreen+ newborn screening v0.1863 HBB Zornitza Stark edited their review of gene: HBB: Changed phenotypes: Sickle cell anaemia, MIM# 603903
BabyScreen+ newborn screening v0.1863 RUNX1 Zornitza Stark Classified gene: RUNX1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1863 RUNX1 Zornitza Stark Gene: runx1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1862 RUNX1 Zornitza Stark edited their review of gene: RUNX1: Changed rating: GREEN
BabyScreen+ newborn screening v0.1862 MCFD2 Zornitza Stark Marked gene: MCFD2 as ready
BabyScreen+ newborn screening v0.1862 MCFD2 Zornitza Stark Gene: mcfd2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1862 MCFD2 Zornitza Stark Tag for review was removed from gene: MCFD2.
Tag treatable tag was added to gene: MCFD2.
BabyScreen+ newborn screening v0.1862 MCFD2 Zornitza Stark reviewed gene: MCFD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor V and factor VIII, combined deficiency of, MIM# 613625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1862 HBB Zornitza Stark Tag for review was removed from gene: HBB.
BabyScreen+ newborn screening v0.1862 HBB Zornitza Stark changed review comment from: Well established gene-disease associations.

Congenital onset.

Both sickle cell anaemia and beta thalassaemia are treatable disorders.

Beta thal: gene therapy (betibeglogene autotemcel - clinical trial), red cell transfusions, bone marrow transplantation (Hematopoietic Stem Cell Transplantation (HSCT)), Luspatercept

Sickle cell: glutamine, voxelotor, crizanlizumab, hydroxyurea, ,red cell transfusions, bone marrow transplantation (Hematopoietic Stem Cell Transplantation (HSCT)), gene therapy (BCH-BB694 BCL11A shmiR lentiviral vector - clinical trial and autologous CRISPR-Cas9-edited CD34+ hematopoietic stem and progenitor cells) - clinical trial)

Some of the beta-that variants are structural -- ability to detect reliably? For review.; to: Well established gene-disease associations.

Congenital onset.

Both sickle cell anaemia and beta thalassaemia are treatable disorders.

Beta thal: gene therapy (betibeglogene autotemcel - clinical trial), red cell transfusions, bone marrow transplantation (Hematopoietic Stem Cell Transplantation (HSCT)), Luspatercept

Sickle cell: glutamine, voxelotor, crizanlizumab, hydroxyurea, ,red cell transfusions, bone marrow transplantation (Hematopoietic Stem Cell Transplantation (HSCT)), gene therapy (BCH-BB694 BCL11A shmiR lentiviral vector - clinical trial and autologous CRISPR-Cas9-edited CD34+ hematopoietic stem and progenitor cells) - clinical trial)

Some of the beta-that variants are structural -- ability to detect reliably? For review.

We are only able to reliably screen for the HbS association.
BabyScreen+ newborn screening v0.1862 HBA2 Zornitza Stark Classified gene: HBA2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1862 HBA2 Zornitza Stark Gene: hba2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1861 HBA2 Zornitza Stark edited their review of gene: HBA2: Changed rating: AMBER
BabyScreen+ newborn screening v0.1861 HBA1 Zornitza Stark Classified gene: HBA1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1861 HBA1 Zornitza Stark Gene: hba1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1860 HBA1 Zornitza Stark changed review comment from: Well established gene-disease association.

Congenital onset.

Treatable: transfusions, bone marrow transplant.

However, there is widespread screening in pregnancy. Also note mutational spectrum includes SVs/CNVs: can we reliably diagnose? For review.; to: Well established gene-disease association.

Congenital onset.

Treatable: transfusions, bone marrow transplant.

However, there is widespread screening in pregnancy. Also note mutational spectrum includes SVs/CNVs: can we reliably diagnose?

Exclude for now due to technical concerns.
BabyScreen+ newborn screening v0.1860 HBA1 Zornitza Stark edited their review of gene: HBA1: Changed rating: AMBER
BabyScreen+ newborn screening v0.1860 F8 Zornitza Stark Classified gene: F8 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1860 F8 Zornitza Stark Gene: f8 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1859 F8 Zornitza Stark changed review comment from: Well established gene-disease association.

Variable severity.

Treatment: recombinant factor VIII. Gene therapy trial.

Non-genetic confirmatory testing: factor VIII levels.

Note: excluded from other screening tests due to concerns regarding ability to detect the intron 22 inversion (Inv22) mutation of F8 which causes about 45% of severe HA cases. For review.; to: Well established gene-disease association.

Variable severity.

Treatment: recombinant factor VIII. Gene therapy trial.

Non-genetic confirmatory testing: factor VIII levels.

Note: excluded from other screening tests due to concerns regarding ability to detect the intron 22 inversion (Inv22) mutation of F8 which causes about 45% of severe HA cases. Intron 1 inversion also common.

Excluded for now until we can confirm we can detect inversion.
BabyScreen+ newborn screening v0.1859 F8 Zornitza Stark edited their review of gene: F8: Changed rating: AMBER
BabyScreen+ newborn screening v0.1859 TMEM43 Zornitza Stark Tag for review was removed from gene: TMEM43.
BabyScreen+ newborn screening v0.1859 LAMP2 Zornitza Stark Tag for review was removed from gene: LAMP2.
BabyScreen+ newborn screening v0.1859 LOX Zornitza Stark Tag for review was removed from gene: LOX.
BabyScreen+ newborn screening v0.1859 TBX1 Zornitza Stark Classified gene: TBX1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1859 TBX1 Zornitza Stark Gene: tbx1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1858 TBX1 Zornitza Stark reviewed gene: TBX1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: DiGeorge syndrome MIM# 188400, Velocardiofacial syndrome MIM# 192430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1858 TBX1 Zornitza Stark Tag for review was removed from gene: TBX1.
BabyScreen+ newborn screening v0.1858 PRKG1 Zornitza Stark Classified gene: PRKG1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1858 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1857 PRKG1 Zornitza Stark Tag for review was removed from gene: PRKG1.
BabyScreen+ newborn screening v0.1857 PRKG1 Zornitza Stark edited their review of gene: PRKG1: Changed rating: GREEN
BabyScreen+ newborn screening v0.1857 MYH11 Zornitza Stark Classified gene: MYH11 as Green List (high evidence)
BabyScreen+ newborn screening v0.1857 MYH11 Zornitza Stark Gene: myh11 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1856 MYH11 Zornitza Stark Tag for review was removed from gene: MYH11.
BabyScreen+ newborn screening v0.1856 MYH11 Zornitza Stark edited their review of gene: MYH11: Changed rating: GREEN
BabyScreen+ newborn screening v0.1856 LOX Zornitza Stark Classified gene: LOX as Green List (high evidence)
BabyScreen+ newborn screening v0.1856 LOX Zornitza Stark Gene: lox has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1855 LOX Zornitza Stark edited their review of gene: LOX: Changed rating: GREEN
BabyScreen+ newborn screening v0.1855 KCNQ1 Zornitza Stark Tag for review was removed from gene: KCNQ1.
BabyScreen+ newborn screening v0.1855 KCNQ1 Zornitza Stark Classified gene: KCNQ1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1855 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1854 KCNQ1 Zornitza Stark edited their review of gene: KCNQ1: Changed rating: GREEN
BabyScreen+ newborn screening v0.1854 DSG2 Zornitza Stark Tag for review was removed from gene: DSG2.
BabyScreen+ newborn screening v0.1854 COL3A1 Zornitza Stark Tag for review was removed from gene: COL3A1.
BabyScreen+ newborn screening v0.1854 JUP Zornitza Stark Mode of inheritance for gene: JUP was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1853 JUP Zornitza Stark Classified gene: JUP as Green List (high evidence)
BabyScreen+ newborn screening v0.1853 JUP Zornitza Stark Gene: jup has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1852 JUP Zornitza Stark Tag for review was removed from gene: JUP.
BabyScreen+ newborn screening v0.1852 JUP Zornitza Stark edited their review of gene: JUP: Added comment: Screen for bi-allelic disease as can be earlier onset, more severe.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1852 DSP Zornitza Stark Mode of inheritance for gene: DSP was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1851 DSP Zornitza Stark Classified gene: DSP as Green List (high evidence)
BabyScreen+ newborn screening v0.1851 DSP Zornitza Stark Gene: dsp has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1850 DSP Zornitza Stark Tag for review was removed from gene: DSP.
BabyScreen+ newborn screening v0.1850 DSP Zornitza Stark edited their review of gene: DSP: Added comment: Screen for bi-allelic disease as can be more severe, earlier onset.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1850 CALM3 Zornitza Stark Phenotypes for gene: CALM3 were changed from Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM# 618782 to Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM# 618782; Long QT syndrome 16, MIM#618782
BabyScreen+ newborn screening v0.1849 CALM3 Zornitza Stark edited their review of gene: CALM3: Added comment: Variants in this gene also cause Long QT syndrome, and other Long QT syndrome genes have been included in the panel.; Changed phenotypes: Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM# 618782, Long QT syndrome 16, MIM#618782
BabyScreen+ newborn screening v0.1849 CALM3 Zornitza Stark Tag for review was removed from gene: CALM3.
BabyScreen+ newborn screening v0.1849 CALM2 Zornitza Stark Tag for review was removed from gene: CALM2.
BabyScreen+ newborn screening v0.1849 LAMP2 Zornitza Stark Tag cardiac tag was added to gene: LAMP2.
BabyScreen+ newborn screening v0.1849 TRPM4 Zornitza Stark Tag cardiac tag was added to gene: TRPM4.
BabyScreen+ newborn screening v0.1849 TMEM43 Zornitza Stark changed review comment from: Rated as 'strong actionability' in paediatric patients by ClinGen together with other ARVC genes.

ARVC is a progressive heart disease characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle, though the left ventricle may also be affected. It is associated with an increased risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) in young individuals and athletes. The VA is usually in proportion to the degree of ventricular remodeling and dysfunction, and electrical instability. The mechanism of SCD is cardiac arrest due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

Age of onset is highly variable with a mean age of diagnosis of 31 years and a range of 4 to 64 years.

Antiarrhythmic drugs and beta-blockers are not recommended in healthy gene carriers. In patients with ARVC and ventricular arrhythmia (VA), a beta-blocker or other antiarrhythmic is recommended.

Recommendations for ICD placement in patients with ARVC differ across guidelines, both in terms of the indications for placement and whether recommendations are based on evidence or expert opinion. Recommendations based on non-randomized studies support ICD placement in patients with ARVC and an additional marker of increased risk of SCD (resuscitated SCA, sustained VT hemodynamically tolerated, and significant ventricular dysfunction with RVEF or LVEF ≤35%) and in patients with ARVC and syncope presumed to be due to VA if meaningful survival greater than 1 year is expected. The presence of a combination of other risk factors (e.g., male sex, frequent PVCs, syncope) may also be used to indicate implantation.

Serial screening for the emergence of cardiomyopathy is recommended for clinically unaffected individuals who carry a variant associated with ARVC, including:

• Medical history, with special attention to heart failure symptoms, arrhythmias, presyncope or syncope, and thromboembolism
• Physical examination with special attention to cardiac and neuromuscular systems and examination of the integumentary system if ARVC is suspected
• Electrocardiography
• Cardiovascular imaging.

Penetrance:
In a study of 264 probands with genetic variants associated with ARVC who presented alive, 73% had sustained VA, 13% had symptomatic HF, and 5% had cardiac death (2% SCD, 2% HF, and 1% HF with VA) during median 8-year follow-up. Among 385 family members of the probands who also carried an ARVC variant, 32% met clinical criteria for ARVC, 11% experienced sustained VA, and 2% died during follow-up (1% from SCD, 0.5% from HF, and 0.5% non-cardiac issues). In a second study of 220 probands with genetic variants associated with ARVC who presented alive, 54% presented with sustained VT. In 321 family members of the probands who also carried an ARVC variant, 14% were symptomatic at presentation but 8% experienced VA during a mean 4-year follow-up. For all 541 cases, 60% met clinical criteria for ARVC, 30% had sustained VA, 14% developed ventricular dysfunction, 5% experienced HF, 4% had a resuscitated SCD/VF, and 2% died over a mean follow-up of 6 years.; to: Rated as 'strong actionability' in paediatric patients by ClinGen together with other ARVC genes.

ARVC is a progressive heart disease characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle, though the left ventricle may also be affected. It is associated with an increased risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) in young individuals and athletes. The VA is usually in proportion to the degree of ventricular remodeling and dysfunction, and electrical instability. The mechanism of SCD is cardiac arrest due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

Age of onset is highly variable with a mean age of diagnosis of 31 years and a range of 4 to 64 years.

Antiarrhythmic drugs and beta-blockers are not recommended in healthy gene carriers. In patients with ARVC and ventricular arrhythmia (VA), a beta-blocker or other antiarrhythmic is recommended.

Recommendations for ICD placement in patients with ARVC differ across guidelines, both in terms of the indications for placement and whether recommendations are based on evidence or expert opinion. Recommendations based on non-randomized studies support ICD placement in patients with ARVC and an additional marker of increased risk of SCD (resuscitated SCA, sustained VT hemodynamically tolerated, and significant ventricular dysfunction with RVEF or LVEF ≤35%) and in patients with ARVC and syncope presumed to be due to VA if meaningful survival greater than 1 year is expected. The presence of a combination of other risk factors (e.g., male sex, frequent PVCs, syncope) may also be used to indicate implantation.

Serial screening for the emergence of cardiomyopathy is recommended for clinically unaffected individuals who carry a variant associated with ARVC, including:

• Medical history, with special attention to heart failure symptoms, arrhythmias, presyncope or syncope, and thromboembolism
• Physical examination with special attention to cardiac and neuromuscular systems and examination of the integumentary system if ARVC is suspected
• Electrocardiography
• Cardiovascular imaging.

Penetrance:
In a study of 264 probands with genetic variants associated with ARVC who presented alive, 73% had sustained VA, 13% had symptomatic HF, and 5% had cardiac death (2% SCD, 2% HF, and 1% HF with VA) during median 8-year follow-up. Among 385 family members of the probands who also carried an ARVC variant, 32% met clinical criteria for ARVC, 11% experienced sustained VA, and 2% died during follow-up (1% from SCD, 0.5% from HF, and 0.5% non-cardiac issues). In a second study of 220 probands with genetic variants associated with ARVC who presented alive, 54% presented with sustained VT. In 321 family members of the probands who also carried an ARVC variant, 14% were symptomatic at presentation but 8% experienced VA during a mean 4-year follow-up. For all 541 cases, 60% met clinical criteria for ARVC, 30% had sustained VA, 14% developed ventricular dysfunction, 5% experienced HF, 4% had a resuscitated SCD/VF, and 2% died over a mean follow-up of 6 years.

Note founder variant in Newfoundland.
BabyScreen+ newborn screening v0.1849 TMEM43 Zornitza Stark edited their review of gene: TMEM43: Changed rating: RED
BabyScreen+ newborn screening v0.1849 SCN5A Zornitza Stark Classified gene: SCN5A as Green List (high evidence)
BabyScreen+ newborn screening v0.1849 SCN5A Zornitza Stark Gene: scn5a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1848 SCN5A Zornitza Stark Tag for review was removed from gene: SCN5A.
BabyScreen+ newborn screening v0.1848 SCN5A Zornitza Stark edited their review of gene: SCN5A: Changed rating: GREEN
BabyScreen+ newborn screening v0.1848 KCNH2 Zornitza Stark Classified gene: KCNH2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1848 KCNH2 Zornitza Stark Gene: kcnh2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1847 KCNH2 Zornitza Stark Tag for review was removed from gene: KCNH2.
BabyScreen+ newborn screening v0.1847 KCNH2 Zornitza Stark edited their review of gene: KCNH2: Changed rating: GREEN
BabyScreen+ newborn screening v0.1847 DSC2 Zornitza Stark Tag for review was removed from gene: DSC2.
BabyScreen+ newborn screening v0.1847 CASQ2 Zornitza Stark Mode of inheritance for gene: CASQ2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1846 CASQ2 Zornitza Stark Classified gene: CASQ2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1846 CASQ2 Zornitza Stark Gene: casq2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1845 CASQ2 Zornitza Stark Tag for review was removed from gene: CASQ2.
BabyScreen+ newborn screening v0.1845 CASQ2 Zornitza Stark changed review comment from: Well established gene-disease association.

ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

For review.; to: Well established gene-disease association.

ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.
BabyScreen+ newborn screening v0.1845 CASQ2 Zornitza Stark edited their review of gene: CASQ2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1845 CASQ2 Zornitza Stark edited their review of gene: CASQ2: Changed rating: GREEN
BabyScreen+ newborn screening v0.1845 ACTA2 Zornitza Stark Classified gene: ACTA2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1845 ACTA2 Zornitza Stark Gene: acta2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1844 ACTA2 Zornitza Stark Tag for review was removed from gene: ACTA2.
BabyScreen+ newborn screening v0.1844 ACTA2 Zornitza Stark edited their review of gene: ACTA2: Changed rating: GREEN
BabyScreen+ newborn screening v0.1844 TRDN Zornitza Stark Tag for review was removed from gene: TRDN.
BabyScreen+ newborn screening v0.1844 TECRL Zornitza Stark Tag for review was removed from gene: TECRL.
BabyScreen+ newborn screening v0.1844 RYR2 Zornitza Stark Tag for review was removed from gene: RYR2.
BabyScreen+ newborn screening v0.1844 CALM1 Zornitza Stark Tag for review was removed from gene: CALM1.
BabyScreen+ newborn screening v0.1844 CAD Zornitza Stark Marked gene: CAD as ready
BabyScreen+ newborn screening v0.1844 CAD Zornitza Stark Gene: cad has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1844 CAD Zornitza Stark Classified gene: CAD as Green List (high evidence)
BabyScreen+ newborn screening v0.1844 CAD Zornitza Stark Gene: cad has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1843 CAD Zornitza Stark gene: CAD was added
gene: CAD was added to gNBS. Sources: Expert list
treatable, metabolic tags were added to gene: CAD.
Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAD were set to 28007989
Phenotypes for gene: CAD were set to Developmental and epileptic encephalopathy 50, MIM# 616457
Review for gene: CAD was set to GREEN
Added comment: Developmental and epileptic encephalopathy-50 (DEE50) is an autosomal recessive progressive neurodegenerative neurometabolic disorder characterized by delayed psychomotor development, early-onset refractory seizures, severe developmental regression, and normocytic anemia. Onset is within the first months or years of life.

Affected children can have a favourable response to treatment with uridine, PMID 28007989
Sources: Expert list
BabyScreen+ newborn screening v0.1842 CA12 Zornitza Stark Marked gene: CA12 as ready
BabyScreen+ newborn screening v0.1842 CA12 Zornitza Stark Gene: ca12 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1842 CA12 Zornitza Stark Classified gene: CA12 as Green List (high evidence)
BabyScreen+ newborn screening v0.1842 CA12 Zornitza Stark Gene: ca12 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1841 CA12 Zornitza Stark gene: CA12 was added
gene: CA12 was added to gNBS. Sources: Expert Review
treatable, metabolic tags were added to gene: CA12.
Mode of inheritance for gene: CA12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CA12 were set to Hyperchlorhidrosis, isolated MIM#143860
Review for gene: CA12 was set to GREEN
Added comment: Glu143Lys found in 4 Israeli Bedouin families. 2 other unrelated families reported with 1 missense (LoF demonstrated), 1 splice (aberrant splicing proven) and 1 fs (protein truncating, not NMD).

Excessive salt wasting in sweat can result in severe infantile hyponatraemic dehydration and hyperkalaemia.

Treatment: sodium chloride supplementation
Sources: Expert Review
BabyScreen+ newborn screening v0.1840 AICDA Zornitza Stark Marked gene: AICDA as ready
BabyScreen+ newborn screening v0.1840 AICDA Zornitza Stark Gene: aicda has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1840 AICDA Zornitza Stark Classified gene: AICDA as Green List (high evidence)
BabyScreen+ newborn screening v0.1840 AICDA Zornitza Stark Gene: aicda has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1839 AICDA Zornitza Stark gene: AICDA was added
gene: AICDA was added to gNBS. Sources: Expert Review
treatable, immunological tags were added to gene: AICDA.
Mode of inheritance for gene: AICDA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AICDA were set to Immunodeficiency with hyper-IgM, type 2, MIM# 605258
Review for gene: AICDA was set to GREEN
Added comment: Hyper-IgM syndrome type 2 (HIGM2) is a rare immunodeficiency characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE, resulting in a profound susceptibility to bacterial infections. Well established gene-disease association.

Severe, congenital disorder.

Treatment: immunoglobulin replacement therapy.

Confirmatory testing: antibody levels.
Sources: Expert Review
BabyScreen+ newborn screening v0.1838 AGPAT2 Zornitza Stark Marked gene: AGPAT2 as ready
BabyScreen+ newborn screening v0.1838 AGPAT2 Zornitza Stark Gene: agpat2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1838 AGPAT2 Zornitza Stark Classified gene: AGPAT2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1838 AGPAT2 Zornitza Stark Gene: agpat2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1837 AGPAT2 Zornitza Stark gene: AGPAT2 was added
gene: AGPAT2 was added to gNBS. Sources: Expert list
for review, treatable, endocrine tags were added to gene: AGPAT2.
Mode of inheritance for gene: AGPAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGPAT2 were set to 29704234
Phenotypes for gene: AGPAT2 were set to Lipodystrophy, congenital generalized, type 1, MIM# 608594
Review for gene: AGPAT2 was set to AMBER
Added comment: Established gene-disease association.

Congenital generalized lipodystrophy (CGL), or Berardinelli-Seip syndrome, is a rare autosomal recessive disease characterized by a near absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biologic features include acanthosis nigricans, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia.

Leptin replacement therapy (metreleptin) has been found to improve metabolic parameters in many patients with lipodystrophy. Metreleptin is approved in the United States as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy and has been submitted for approval elsewhere.

For review regarding availability and use of treatment locally.
Sources: Expert list
BabyScreen+ newborn screening v0.1836 APC Zornitza Stark Classified gene: APC as Red List (low evidence)
BabyScreen+ newborn screening v0.1836 APC Zornitza Stark Gene: apc has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1835 APC Zornitza Stark Tag cancer tag was added to gene: APC.
BabyScreen+ newborn screening v0.1835 WT1 Zornitza Stark Classified gene: WT1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1835 WT1 Zornitza Stark Gene: wt1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1834 WT1 Zornitza Stark Tag for review was removed from gene: WT1.
BabyScreen+ newborn screening v0.1834 WT1 Zornitza Stark changed review comment from: Rated as 'moderate actionability' in paediatric patients by ClinGen.

Individuals with germline WT1 pathogenic variants are more likely to have bilateral or multicentric tumors and to develop tumors at an early age. The median age of diagnosis is between 3 and 4 years and both kidneys are affected in ~5% of children. Significantly more females than males have the bilateral disease. Adult forms are very rare. In the majority of cases, the prognosis is favorable with a survival rate of over 90%.

The goal of surveillance in individuals with a genetic predisposition to WT is to

detect tumors while they are low-stage and require less treatment compared to advanced-stage tumors. Surveillance is not a one-time event and should continue through the period of risk. WTs can double in size every week, leading to the recommendation that evaluation with abdominal ultrasound be performed every 3-4 months, with and no less frequently than 3 times a year, until age five years. Even at this frequency, occasional tumors may present clinically between scans and families should be made aware of this. However, there is no evidence to suggest that such tumors have a worse outcome.

No evidence was found on the effectiveness of surveillance in children with WT due to WT1 pathogenic variants. In addition, there is no clear evidence that surveillance results in a significant decrease in mortality or tumor stage generally. However, tumors detected by surveillance would be anticipated to be on average smaller than tumors that present clinically. There have been three small retrospective evaluations of WT surveillance published, only one of which reported a significant difference in stage distribution between screened and unscreened individuals. This report was a case series of children with Beckwith-Wiedemann syndrome and idiopathic hemihypertropy, where 0/12 screened children with WT had late-stage disease and 25/59 (42%) of unscreened children had late-stage WT (p<0.003). In addition, in Germany, where abdominal ultrasound in children is common and 10% of WT are diagnosed prior to symptoms, there are some data to suggest that asymptomatic tumors are of lower stage than those present due to clinical symptoms.

Penetrance is unclear. For review.; to: Rated as 'moderate actionability' in paediatric patients by ClinGen.

Individuals with germline WT1 pathogenic variants are more likely to have bilateral or multicentric tumors and to develop tumors at an early age. The median age of diagnosis is between 3 and 4 years and both kidneys are affected in ~5% of children. Significantly more females than males have the bilateral disease. Adult forms are very rare. In the majority of cases, the prognosis is favorable with a survival rate of over 90%.

The goal of surveillance in individuals with a genetic predisposition to WT is to

detect tumors while they are low-stage and require less treatment compared to advanced-stage tumors. Surveillance is not a one-time event and should continue through the period of risk. WTs can double in size every week, leading to the recommendation that evaluation with abdominal ultrasound be performed every 3-4 months, with and no less frequently than 3 times a year, until age five years. Even at this frequency, occasional tumors may present clinically between scans and families should be made aware of this. However, there is no evidence to suggest that such tumors have a worse outcome.

No evidence was found on the effectiveness of surveillance in children with WT due to WT1 pathogenic variants. In addition, there is no clear evidence that surveillance results in a significant decrease in mortality or tumor stage generally. However, tumors detected by surveillance would be anticipated to be on average smaller than tumors that present clinically. There have been three small retrospective evaluations of WT surveillance published, only one of which reported a significant difference in stage distribution between screened and unscreened individuals. This report was a case series of children with Beckwith-Wiedemann syndrome and idiopathic hemihypertropy, where 0/12 screened children with WT had late-stage disease and 25/59 (42%) of unscreened children had late-stage WT (p<0.003). In addition, in Germany, where abdominal ultrasound in children is common and 10% of WT are diagnosed prior to symptoms, there are some data to suggest that asymptomatic tumors are of lower stage than those present due to clinical symptoms.
BabyScreen+ newborn screening v0.1834 GLA Zornitza Stark Tag for review was removed from gene: GLA.
BabyScreen+ newborn screening v0.1834 GLA Zornitza Stark changed review comment from: Assessed as 'moderate actionability' in paediatric patients by ClinGen.

In classic FD, the first symptoms, including chronic neuropathic pain and episodic severe pain crises, emerge during childhood (typically age 3-10 years). Heterozygous females typically have a later median age of onset than males (9-13 years versus 13-23 years). Rarely, females may be relatively asymptomatic and have a normal life span or may have symptoms as severe as males with the classic phenotype.

Cardiac and/or cerebrovascular disease is present in most males by middle age while ESRD usually develops during the third to fifth decade. Renal and cardiac failure represent major sources of morbidity, and account for the reduced lifespan among affected males (50-58 years) and females (70-75 years) compared to the normal population.

A systematic review of RCTs of ERT reported on nine studies of 351 FD patients; however, many of these studies reported only on the effect of ERT on levels of enzyme substrate. Data from 2 trials (n=39 males) found no statistically significant differences in plasma enzyme substrate and one trial (n=24 males) found no statistical differences in renal function between individuals treated with agalsidase alfa and placebo (up to 6-month follow-up). Similar results were seen for agalsidase beta. One trial of 26 male patients found a statistically significant difference in pain, favoring agalsidase alfa compared to placebo at 5-6 months after treatment. No trial reported on the effect of agalsidase alfa on mortality or cardiac/cerebrovascular disease. One trial of agalsidase beta (n=82 males and females) found no difference in mortality, renal function, or symptoms or complications of cardiac or cerebrovascular disease over 18 months. The long-term influence of ERT on risk of morbidity and mortality related to FD remains to be established.

Migalastat, an oral chaperone drug, is recommended as an option for treatment for some patients with FD who are over 16 years with an amenable genetic variant who would usually be offered ERT. For non-amenable genotypes, migalastat may result in a net loss of alpha-Gal A activity, potentially worsening the disease condition.

A systematic review evaluated 2 phase III RCTs that both included males and females. One RCT randomized patients to switch from ERT to migalastat (n = 36) or continue with ERT (n = 24) during an 18-month period with a 12-month extension in which all patients received migalastat. During the treatment period, the percentage of patients who had a renal, cardiac, or cerebrovascular event or died was 29% of patients on migalastat compared to 44% of patients on ERT. However, this difference was not statistically significant. A second RCT compared migalastat (n=34) with placebo (n=33) over a 6-month period, with an 18-month extension study. The primary outcome was change from baseline in interstitial capillary inclusions of the enzyme substrate globotriaosylceramide (GL-3), which was not significantly different between groups. Results from both trials indicate that migalastat does not have a significant beneficial effect on pain, health-related quality of life outcomes, or glomerular filtration rate (results were uncertain due to large confidence intervals, small sample sizes, and/or short follow-up time). Migalastat did not influence left ventricular ejection fraction but did improve left ventricular mass over 18 months.

There are a number of recommendations for surveillance and agents to avoid (amiodarone). There is no consensus as to when ERT should be started.; to: Assessed as 'moderate actionability' in paediatric patients by ClinGen.

In classic FD, the first symptoms, including chronic neuropathic pain and episodic severe pain crises, emerge during childhood (typically age 3-10 years). Heterozygous females typically have a later median age of onset than males (9-13 years versus 13-23 years). Rarely, females may be relatively asymptomatic and have a normal life span or may have symptoms as severe as males with the classic phenotype.

Cardiac and/or cerebrovascular disease is present in most males by middle age while ESRD usually develops during the third to fifth decade. Renal and cardiac failure represent major sources of morbidity, and account for the reduced lifespan among affected males (50-58 years) and females (70-75 years) compared to the normal population.

A systematic review of RCTs of ERT reported on nine studies of 351 FD patients; however, many of these studies reported only on the effect of ERT on levels of enzyme substrate. Data from 2 trials (n=39 males) found no statistically significant differences in plasma enzyme substrate and one trial (n=24 males) found no statistical differences in renal function between individuals treated with agalsidase alfa and placebo (up to 6-month follow-up). Similar results were seen for agalsidase beta. One trial of 26 male patients found a statistically significant difference in pain, favoring agalsidase alfa compared to placebo at 5-6 months after treatment. No trial reported on the effect of agalsidase alfa on mortality or cardiac/cerebrovascular disease. One trial of agalsidase beta (n=82 males and females) found no difference in mortality, renal function, or symptoms or complications of cardiac or cerebrovascular disease over 18 months. The long-term influence of ERT on risk of morbidity and mortality related to FD remains to be established.

Migalastat, an oral chaperone drug, is recommended as an option for treatment for some patients with FD who are over 16 years with an amenable genetic variant who would usually be offered ERT. For non-amenable genotypes, migalastat may result in a net loss of alpha-Gal A activity, potentially worsening the disease condition.

A systematic review evaluated 2 phase III RCTs that both included males and females. One RCT randomized patients to switch from ERT to migalastat (n = 36) or continue with ERT (n = 24) during an 18-month period with a 12-month extension in which all patients received migalastat. During the treatment period, the percentage of patients who had a renal, cardiac, or cerebrovascular event or died was 29% of patients on migalastat compared to 44% of patients on ERT. However, this difference was not statistically significant. A second RCT compared migalastat (n=34) with placebo (n=33) over a 6-month period, with an 18-month extension study. The primary outcome was change from baseline in interstitial capillary inclusions of the enzyme substrate globotriaosylceramide (GL-3), which was not significantly different between groups. Results from both trials indicate that migalastat does not have a significant beneficial effect on pain, health-related quality of life outcomes, or glomerular filtration rate (results were uncertain due to large confidence intervals, small sample sizes, and/or short follow-up time). Migalastat did not influence left ventricular ejection fraction but did improve left ventricular mass over 18 months.

There are a number of recommendations for surveillance and agents to avoid (amiodarone). There is no consensus as to when ERT should be started. Note ERT is licensed in Australia from age 7 years.

However, carbamazepine relieves neuropathic pain, which has onset in early childhood. Overall, include.
BabyScreen+ newborn screening v0.1834 GLA Zornitza Stark edited their review of gene: GLA: Changed rating: GREEN
BabyScreen+ newborn screening v0.1834 SMAD2 Zornitza Stark Marked gene: SMAD2 as ready
BabyScreen+ newborn screening v0.1834 SMAD2 Zornitza Stark Gene: smad2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1834 SMAD2 Zornitza Stark Classified gene: SMAD2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1834 SMAD2 Zornitza Stark Gene: smad2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1833 SMAD2 Zornitza Stark Tag cardiac tag was added to gene: SMAD2.
Tag treatable tag was added to gene: SMAD2.
BabyScreen+ newborn screening v0.1833 SMAD2 Zornitza Stark gene: SMAD2 was added
gene: SMAD2 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: SMAD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMAD2 were set to Loeys-Dietz syndrome 6, MIM# 619656
Review for gene: SMAD2 was set to GREEN
Added comment: 9 individuals from 5 unrelated families reported with LDS phenotype. Gene-disease association rated 'moderate' by ClinGen but this gene is included in our diagnostic testing.

LDS included in gNBS panel as in general medical actionability for the LDS group of disorders is considered established.

Can manifest in early childhood.

Treatment: different interventions, including beta-blockers, surgical and monitoring

Non-genetic confirmatory test: characteristic clinical findings
Sources: Expert Review
BabyScreen+ newborn screening v0.1832 SMAD3 Zornitza Stark Tag for review was removed from gene: SMAD3.
Tag treatable tag was added to gene: SMAD3.
BabyScreen+ newborn screening v0.1832 TGFB3 Zornitza Stark Tag for review was removed from gene: TGFB3.
BabyScreen+ newborn screening v0.1832 TGFB2 Zornitza Stark Tag for review was removed from gene: TGFB2.
BabyScreen+ newborn screening v0.1832 PMS2 Zornitza Stark Classified gene: PMS2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1832 PMS2 Zornitza Stark Gene: pms2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1831 PMS2 Zornitza Stark Tag for review was removed from gene: PMS2.
BabyScreen+ newborn screening v0.1831 PMS2 Zornitza Stark edited their review of gene: PMS2: Changed rating: GREEN
BabyScreen+ newborn screening v0.1831 MSH6 Zornitza Stark Classified gene: MSH6 as Green List (high evidence)
BabyScreen+ newborn screening v0.1831 MSH6 Zornitza Stark Gene: msh6 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1830 MSH6 Zornitza Stark Tag for review was removed from gene: MSH6.
BabyScreen+ newborn screening v0.1830 MSH6 Zornitza Stark edited their review of gene: MSH6: Changed rating: GREEN
BabyScreen+ newborn screening v0.1830 MSH2 Zornitza Stark Classified gene: MSH2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1830 MSH2 Zornitza Stark Gene: msh2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1829 MSH2 Zornitza Stark Tag for review was removed from gene: MSH2.
BabyScreen+ newborn screening v0.1829 MSH2 Zornitza Stark edited their review of gene: MSH2: Changed rating: GREEN
BabyScreen+ newborn screening v0.1829 MLH1 Zornitza Stark Classified gene: MLH1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1829 MLH1 Zornitza Stark Gene: mlh1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1828 MLH1 Zornitza Stark edited their review of gene: MLH1: Changed rating: GREEN
BabyScreen+ newborn screening v0.1828 SLC13A5 Zornitza Stark Classified gene: SLC13A5 as Red List (low evidence)
BabyScreen+ newborn screening v0.1828 SLC13A5 Zornitza Stark Gene: slc13a5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1827 PTCH1 Zornitza Stark Classified gene: PTCH1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1827 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1826 PTCH1 Zornitza Stark Tag for review was removed from gene: PTCH1.
BabyScreen+ newborn screening v0.1826 PMM2 Zornitza Stark Classified gene: PMM2 as Red List (low evidence)
BabyScreen+ newborn screening v0.1826 PMM2 Zornitza Stark Gene: pmm2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1825 PMM2 Zornitza Stark changed review comment from: Well established gene-disease association.

Two clinical presentations - solely neurologic form and a neurologic-multivisceral form
Mortality approximately 20% in first 2 years

Treatment: epalrestat

PMID 31636082: Epalrestat increased PMM2 enzymatic activity in four PMM2-CDG patient fibroblast lines with genotypes R141H/F119L, R141H/E139K, R141H/N216I and R141H/F183S. PMM2 enzyme activity gains ranged from 30% to 400% over baseline, depending on genotype. Pharmacological inhibition of aldose reductase by epalrestat may shunt glucose from the polyol pathway to glucose-1,6-bisphosphate, which is an endogenous stabilizer and coactivator of PMM2 homodimerization. Epalrestat is a safe, oral and brain penetrant drug that was approved 27 years ago in Japan to treat diabetic neuropathy in geriatric populations.

For review: uncertain if in use for CDG; to: Well established gene-disease association.

Two clinical presentations - solely neurologic form and a neurologic-multivisceral form
Mortality approximately 20% in first 2 years

Treatment: epalrestat

PMID 31636082: Epalrestat increased PMM2 enzymatic activity in four PMM2-CDG patient fibroblast lines with genotypes R141H/F119L, R141H/E139K, R141H/N216I and R141H/F183S. PMM2 enzyme activity gains ranged from 30% to 400% over baseline, depending on genotype. Pharmacological inhibition of aldose reductase by epalrestat may shunt glucose from the polyol pathway to glucose-1,6-bisphosphate, which is an endogenous stabilizer and coactivator of PMM2 homodimerization. Epalrestat is a safe, oral and brain penetrant drug that was approved 27 years ago in Japan to treat diabetic neuropathy in geriatric populations.

Treatment not well established in patients.
BabyScreen+ newborn screening v0.1825 PMM2 Zornitza Stark edited their review of gene: PMM2: Changed rating: RED
BabyScreen+ newborn screening v0.1825 PMM2 Zornitza Stark Tag for review was removed from gene: PMM2.
Tag metabolic was removed from gene: PMM2.
BabyScreen+ newborn screening v0.1825 PIK3CA Zornitza Stark Classified gene: PIK3CA as Red List (low evidence)
BabyScreen+ newborn screening v0.1825 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1824 PIK3CA Zornitza Stark Tag for review was removed from gene: PIK3CA.
BabyScreen+ newborn screening v0.1824 PIK3CA Zornitza Stark edited their review of gene: PIK3CA: Changed rating: RED
BabyScreen+ newborn screening v0.1824 MEN1 Zornitza Stark Tag for review was removed from gene: MEN1.
BabyScreen+ newborn screening v0.1824 HPRT1 Zornitza Stark Classified gene: HPRT1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1824 HPRT1 Zornitza Stark Gene: hprt1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1823 HPRT1 Zornitza Stark changed review comment from: Uncertain if these are essentially symptomatic treatments.; to: Symptomatic treatments.
BabyScreen+ newborn screening v0.1823 HPRT1 Zornitza Stark edited their review of gene: HPRT1: Changed rating: RED
BabyScreen+ newborn screening v0.1823 GLDC Zornitza Stark Tag for review was removed from gene: GLDC.
Tag treatable tag was added to gene: GLDC.
Tag metabolic tag was added to gene: GLDC.
BabyScreen+ newborn screening v0.1823 GLDC Zornitza Stark edited their review of gene: GLDC: Changed rating: GREEN
BabyScreen+ newborn screening v0.1823 FBN1 Zornitza Stark Classified gene: FBN1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1823 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1822 FBN1 Zornitza Stark Tag for review was removed from gene: FBN1.
Tag cardiac tag was added to gene: FBN1.
Tag treatable tag was added to gene: FBN1.
BabyScreen+ newborn screening v0.1822 FBN1 Zornitza Stark edited their review of gene: FBN1: Changed rating: GREEN
BabyScreen+ newborn screening v0.1822 DICER1 Zornitza Stark Classified gene: DICER1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1822 DICER1 Zornitza Stark Gene: dicer1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1821 DICER1 Zornitza Stark Tag for review was removed from gene: DICER1.
BabyScreen+ newborn screening v0.1821 DICER1 Zornitza Stark edited their review of gene: DICER1: Changed rating: GREEN
BabyScreen+ newborn screening v0.1821 TP53 Zornitza Stark Tag for review was removed from gene: TP53.
BabyScreen+ newborn screening v0.1821 SLC5A6 Zornitza Stark Tag for review was removed from gene: SLC5A6.
Tag treatable tag was added to gene: SLC5A6.
Tag metabolic tag was added to gene: SLC5A6.
BabyScreen+ newborn screening v0.1821 RET Zornitza Stark Tag for review was removed from gene: RET.
BabyScreen+ newborn screening v0.1821 RET Zornitza Stark changed review comment from: Established gene-disease associations.

Assessed as 'strong actionability' in paediatric patients by ClinGen.

Onset of MEN2A is typically prior to age 35, usually between ages 5 and 25. MTC is generally the first manifestation in MEN2A with probands presenting with a neck mass or neck pain. Metastatic spread is common. MTC is the most common cause of death in patients with MEN2A.

PHEOs usually present after MTC or concomitantly but are the first manifestation in 13-27% of individuals; they occur in about 50% of individuals. PHEOs are diagnosed at an earlier age, have subtler symptoms, and are more likely to be bilateral than sporadic tumors, with malignant transformation occurring in about 4% of cases. Even without malignant progression, PHEOs can be lethal from intractable hypertension or anesthesia-induced hypertensive crises. Depending on the risk category of the RET pathogenic variant, PHEOs have been observed as early as 5 years of age.

For MEN2A children with a “high-risk” pathogenic variant, patients should undergo annual ultrasound and screening for increased calcitonin levels starting at 3 years of age and proceed to thyroidectomy when elevated levels are detected or at 5 years of age. For patients with a “moderate-risk” pathogenic variant, considering the clinical variability of disease expression in family members in this category, annual physical examination, cervical US, and measurement of serum calcitonin levels, should begin at 5 years of age.

Biochemical surveillance for PHPT should begin at 11 years and 16 years of age for patients with high- and moderate-risk variants, respectively; this screening is recommended annually for “high-risk” patients and at least every 2-3 years in “moderate-risk” patients.

Biochemical screening for PHEO should begin at age 11 for patients with high-risk variants and age 16 for patients with moderate-risk variants.

For review: actionable in first 5 years of life?; to: Established gene-disease associations.

Assessed as 'strong actionability' in paediatric patients by ClinGen.

Onset of MEN2A is typically prior to age 35, usually between ages 5 and 25. MTC is generally the first manifestation in MEN2A with probands presenting with a neck mass or neck pain. Metastatic spread is common. MTC is the most common cause of death in patients with MEN2A.

PHEOs usually present after MTC or concomitantly but are the first manifestation in 13-27% of individuals; they occur in about 50% of individuals. PHEOs are diagnosed at an earlier age, have subtler symptoms, and are more likely to be bilateral than sporadic tumors, with malignant transformation occurring in about 4% of cases. Even without malignant progression, PHEOs can be lethal from intractable hypertension or anesthesia-induced hypertensive crises. Depending on the risk category of the RET pathogenic variant, PHEOs have been observed as early as 5 years of age.

For MEN2A children with a “high-risk” pathogenic variant, patients should undergo annual ultrasound and screening for increased calcitonin levels starting at 3 years of age and proceed to thyroidectomy when elevated levels are detected or at 5 years of age. For patients with a “moderate-risk” pathogenic variant, considering the clinical variability of disease expression in family members in this category, annual physical examination, cervical US, and measurement of serum calcitonin levels, should begin at 5 years of age.

Biochemical surveillance for PHPT should begin at 11 years and 16 years of age for patients with high- and moderate-risk variants, respectively; this screening is recommended annually for “high-risk” patients and at least every 2-3 years in “moderate-risk” patients.

Biochemical screening for PHEO should begin at age 11 for patients with high-risk variants and age 16 for patients with moderate-risk variants.

For review: some actionability in first 5 years, variants can be stratified in terms of risk.
BabyScreen+ newborn screening v0.1821 RB1 Zornitza Stark Tag for review was removed from gene: RB1.
BabyScreen+ newborn screening v0.1821 PRKAR1A Zornitza Stark Tag for review was removed from gene: PRKAR1A.
BabyScreen+ newborn screening v0.1821 NF1 Zornitza Stark Classified gene: NF1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1821 NF1 Zornitza Stark Gene: nf1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1820 NF1 Zornitza Stark changed review comment from: For review: does this meet the definition of 'treatable'?; to: Mainly surveillance.
BabyScreen+ newborn screening v0.1820 NF1 Zornitza Stark edited their review of gene: NF1: Changed rating: RED
BabyScreen+ newborn screening v0.1820 MCEE Zornitza Stark Tag for review was removed from gene: MCEE.
BabyScreen+ newborn screening v0.1820 ECHS1 Zornitza Stark Marked gene: ECHS1 as ready
BabyScreen+ newborn screening v0.1820 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1820 ECHS1 Zornitza Stark Classified gene: ECHS1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1820 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1819 ECHS1 Zornitza Stark gene: ECHS1 was added
gene: ECHS1 was added to gNBS. Sources: Expert list
treatable, metabolic tags were added to gene: ECHS1.
Mode of inheritance for gene: ECHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECHS1 were set to 32642440
Phenotypes for gene: ECHS1 were set to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency MIM# 616277
Review for gene: ECHS1 was set to GREEN
Added comment: Well established gene-disease association.

Usually presents in infancy.

Treatable-ID – level 4 evidence: valine restriction improves psychomotor/cognitive development/IQ; improves neurological manifestations (incl. neuro-imaging); improves systemic manifestations (PMID: 32642440)
Sources: Expert list
BabyScreen+ newborn screening v0.1818 DHFR Zornitza Stark Marked gene: DHFR as ready
BabyScreen+ newborn screening v0.1818 DHFR Zornitza Stark Gene: dhfr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1818 DHFR Zornitza Stark Classified gene: DHFR as Green List (high evidence)
BabyScreen+ newborn screening v0.1818 DHFR Zornitza Stark Gene: dhfr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1817 DHFR Zornitza Stark gene: DHFR was added
gene: DHFR was added to gNBS. Sources: Expert Review
treatable, metabolic tags were added to gene: DHFR.
Mode of inheritance for gene: DHFR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DHFR were set to Megaloblastic anaemia due to dihydrofolate reductase deficiency, MIM# 613839
Review for gene: DHFR was set to GREEN
Added comment: Established gene-disease association.

Congenital onset.

Treatment: folinic acid.

Non-genetic confirmatory testing: complete blood count with MCV and CSF 5-methyltetrahydrofolate level.
Sources: Expert Review
BabyScreen+ newborn screening v0.1816 DNAJC12 Zornitza Stark Marked gene: DNAJC12 as ready
BabyScreen+ newborn screening v0.1816 DNAJC12 Zornitza Stark Gene: dnajc12 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1816 DNAJC12 Zornitza Stark Classified gene: DNAJC12 as Green List (high evidence)
BabyScreen+ newborn screening v0.1816 DNAJC12 Zornitza Stark Gene: dnajc12 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1815 DNAJC12 Zornitza Stark gene: DNAJC12 was added
gene: DNAJC12 was added to gNBS. Sources: Expert Review
treatable, metabolic tags were added to gene: DNAJC12.
Mode of inheritance for gene: DNAJC12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAJC12 were set to Hyperphenylalaninemia, mild, non-BH4-deficient, MIM#617384
Review for gene: DNAJC12 was set to GREEN
Added comment: Established gene-disease association.

Manifests as mild hyperphenylalaninaemia that would be detected on NBS – untreated results in axial hypotonia, dystonia, nystagmus, global developmental delay,
and intellectual disability.

From Treatable-ID, level 4 evidence that BH4, L-dopa + carbidopa +/-, 5-
hydroxytryptophan improves psychomotor/cognitive development/IQ; prevents, halts, or slows clinical deterioration and improves neurological manifestations.
Sources: Expert Review
BabyScreen+ newborn screening v0.1814 GALM Zornitza Stark Marked gene: GALM as ready
BabyScreen+ newborn screening v0.1814 GALM Zornitza Stark Gene: galm has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1814 GALM Zornitza Stark Classified gene: GALM as Green List (high evidence)
BabyScreen+ newborn screening v0.1814 GALM Zornitza Stark Gene: galm has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1813 GALM Zornitza Stark gene: GALM was added
gene: GALM was added to gNBS. Sources: Expert Review
treatable, metabolic tags were added to gene: GALM.
Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALM were set to Galactosemia IV MIM#618881
Review for gene: GALM was set to GREEN
Added comment: Established gene-disease association.

Congenital onset.

Treatment: galactose/lactose-restricted diet.

Non-genetic confirmatory testing: galactose level.
Sources: Expert Review
BabyScreen+ newborn screening v0.1812 GCH1 Zornitza Stark Marked gene: GCH1 as ready
BabyScreen+ newborn screening v0.1812 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1812 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Dystonia, dopa-responsive to Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230
BabyScreen+ newborn screening v0.1811 GCH1 Zornitza Stark Publications for gene: GCH1 were set to
BabyScreen+ newborn screening v0.1810 GCH1 Zornitza Stark Mode of inheritance for gene: GCH1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1809 GCH1 Zornitza Stark Classified gene: GCH1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1809 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1808 GCH1 Zornitza Stark Tag treatable tag was added to gene: GCH1.
Tag metabolic tag was added to gene: GCH1.
BabyScreen+ newborn screening v0.1808 GCH1 Zornitza Stark reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910, Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1807 PMS2 Zornitza Stark Marked gene: PMS2 as ready
BabyScreen+ newborn screening v0.1807 PMS2 Zornitza Stark Gene: pms2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1807 PMS2 Zornitza Stark Phenotypes for gene: PMS2 were changed from Lynch syndrome to Mismatch repair cancer syndrome 4, MIM# 619101
BabyScreen+ newborn screening v0.1806 PMS2 Zornitza Stark Mode of inheritance for gene: PMS2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1805 PMS2 Zornitza Stark Classified gene: PMS2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1805 PMS2 Zornitza Stark Gene: pms2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1804 PMS2 Zornitza Stark Tag for review tag was added to gene: PMS2.
Tag cancer tag was added to gene: PMS2.
Tag treatable tag was added to gene: PMS2.
BabyScreen+ newborn screening v0.1804 PMS2 Zornitza Stark reviewed gene: PMS2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mismatch repair cancer syndrome 4, MIM# 619101; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1804 MSH6 Zornitza Stark Marked gene: MSH6 as ready
BabyScreen+ newborn screening v0.1804 MSH6 Zornitza Stark Gene: msh6 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1804 MSH6 Zornitza Stark Phenotypes for gene: MSH6 were changed from Lynch syndrome to Mismatch repair cancer syndrome 3, MIM# 619097
BabyScreen+ newborn screening v0.1803 MSH6 Zornitza Stark Mode of inheritance for gene: MSH6 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1802 MSH6 Zornitza Stark Classified gene: MSH6 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1802 MSH6 Zornitza Stark Gene: msh6 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1801 MSH6 Zornitza Stark Tag for review tag was added to gene: MSH6.
Tag cancer tag was added to gene: MSH6.
Tag treatable tag was added to gene: MSH6.
BabyScreen+ newborn screening v0.1801 MSH6 Zornitza Stark reviewed gene: MSH6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mismatch repair cancer syndrome 3, MIM# 619097; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1801 MLH1 Zornitza Stark changed review comment from: Note mono-allelic variants are associated with adult-onset cancer risk.

MMRCS rated as 'strong actionability' in paediatric patients by ClinGen.

The hallmark of MMRCS is early onset cancer, most often in childhood or young adulthood. The median age of onset of the first tumor is 7.5 years, with a wide range observed (0.4-39 years). A large portion (up to 40%) of patients develop metachronous second malignancies. The median survival after diagnosis of the primary tumor is less than 30 months. Prognosis depends on the possibility of complete resection, making early detection paramount. It is unclear what tumor spectrum will emerge among adults with MMRCS. Brain tumors are frequent and often diagnosed in the first decade of life. The rate of progression appears to be rapid in the brain tumors. The median age at diagnosis of brain tumors is 9 years (range, 2-40 years). Brain tumors are by far the most common cause of death. Colonic adenomatous oligopolyposis typically is diagnosed between 5 and 10 years of age. The progression of adenomas to malignancy in MMRCS is the most rapid of any inherited colorectal cancer syndrome. Among MMRCS patients presenting with colorectal cancer (CRC), the median age at diagnosis was 16 years (range, 8-48 years) with more than half of patients classified as pediatric-onset CRC. The age of onset of small-bowel adenomas is later; they typically develop in the second decade of life. The median age at diagnosis of small-bowel cancer was 28 years, with a range of 11-42 years. The lifetime risk of gastrointestinal cancer among MMRCS patients is the highest reported of all gastrointestinal cancer predisposition syndromes as a function of age. The median age at diagnosis of hematologic malignancy is 6.6 years. Endometrial cancer has been diagnosed between 19 and 44 years. The age at diagnosis of urinary tract tumors has ranged from 10 to 22 years.

The management of MMRCS is based on the current estimates of neoplasia risk and the early age of onset for the cancers, which have led to tentative guidelines for the management of these patients. The age at which to begin surveillance varies by guideline and is represented below as age ranges. In patients with MMRCS, the following surveillance is suggested:

•Screening for CRC by colonoscopy is recommended annually beginning at age 6 to 8 years. Once polyps are identified, colonoscopy every 6 months is recommended.
•Annual surveillance for small-bowel cancer by upper endoscopy and video capsule endoscopy is suggested beginning at 8 to 10 years of age. Monitoring of hemoglobin levels every 6 months also is suggested, beginning at 8 years of age.
•Surveillance for brain tumors by brain MRI every 6 to 12 months is suggested starting at the time of diagnosis even in the first year of life to age 2 years.
•Currently, no proven surveillance modalities for leukemia or lymphoma have been identified. Complete blood count to screen for leukemia is suggested every 6 months beginning at 1 year of age. Clinical examinations and abdominal ultrasounds to screen for lymphoma every 6 months may be considered by the treating physician.
•For individuals with a uterus, surveillance for endometrial cancer is suggested by transvaginal ultrasound, pelvic examination, and endometrial sampling annually starting at age 20 years.
•Surveillance for cancer of the urinary tract is suggested, with annual urinalysis starting at age 10 to 20 years.
•To screen for other types of tumors, whole-body MRI could be considered once a year starting at 6 years of age or when anesthesia is not needed. This method should not replace the need for ultrasound and brain MRI.

Estimated penetrance in MMRCS:

•50% develop small-bowel adenomas
•>90% develop colorectal adenomas
•59 to 70% develop colorectal cancer
•58 to 70% develop high-grade brain tumours
•20-40% develop lymphoma
•10-40% develop leukemia
•10 to 18% develop small-bowel cancer
•<10% develop endometrial cancer
•<10% develop urinary tract cancer

•<10% develop cancer of other sites; to: Note mono-allelic variants are associated with adult-onset cancer risk.

MMRCS rated as 'strong actionability' in paediatric patients by ClinGen.

The hallmark of MMRCS is early onset cancer, most often in childhood or young adulthood. The median age of onset of the first tumor is 7.5 years, with a wide range observed (0.4-39 years). A large portion (up to 40%) of patients develop metachronous second malignancies. The median survival after diagnosis of the primary tumor is less than 30 months. Prognosis depends on the possibility of complete resection, making early detection paramount. It is unclear what tumor spectrum will emerge among adults with MMRCS. Brain tumors are frequent and often diagnosed in the first decade of life. The rate of progression appears to be rapid in the brain tumors. The median age at diagnosis of brain tumors is 9 years (range, 2-40 years). Brain tumors are by far the most common cause of death. Colonic adenomatous oligopolyposis typically is diagnosed between 5 and 10 years of age. The progression of adenomas to malignancy in MMRCS is the most rapid of any inherited colorectal cancer syndrome. Among MMRCS patients presenting with colorectal cancer (CRC), the median age at diagnosis was 16 years (range, 8-48 years) with more than half of patients classified as pediatric-onset CRC. The age of onset of small-bowel adenomas is later; they typically develop in the second decade of life. The median age at diagnosis of small-bowel cancer was 28 years, with a range of 11-42 years. The lifetime risk of gastrointestinal cancer among MMRCS patients is the highest reported of all gastrointestinal cancer predisposition syndromes as a function of age. The median age at diagnosis of hematologic malignancy is 6.6 years. Endometrial cancer has been diagnosed between 19 and 44 years. The age at diagnosis of urinary tract tumors has ranged from 10 to 22 years.

The management of MMRCS is based on the current estimates of neoplasia risk and the early age of onset for the cancers, which have led to tentative guidelines for the management of these patients. The age at which to begin surveillance varies by guideline and is represented below as age ranges. In patients with MMRCS, the following surveillance is suggested:

•Screening for CRC by colonoscopy is recommended annually beginning at age 6 to 8 years. Once polyps are identified, colonoscopy every 6 months is recommended.
•Annual surveillance for small-bowel cancer by upper endoscopy and video capsule endoscopy is suggested beginning at 8 to 10 years of age. Monitoring of hemoglobin levels every 6 months also is suggested, beginning at 8 years of age.
•Surveillance for brain tumors by brain MRI every 6 to 12 months is suggested starting at the time of diagnosis even in the first year of life to age 2 years.
•Currently, no proven surveillance modalities for leukemia or lymphoma have been identified. Complete blood count to screen for leukemia is suggested every 6 months beginning at 1 year of age. Clinical examinations and abdominal ultrasounds to screen for lymphoma every 6 months may be considered by the treating physician.
•For individuals with a uterus, surveillance for endometrial cancer is suggested by transvaginal ultrasound, pelvic examination, and endometrial sampling annually starting at age 20 years.
•Surveillance for cancer of the urinary tract is suggested, with annual urinalysis starting at age 10 to 20 years.
•To screen for other types of tumors, whole-body MRI could be considered once a year starting at 6 years of age or when anesthesia is not needed. This method should not replace the need for ultrasound and brain MRI.

Estimated penetrance in MMRCS:

•50% develop small-bowel adenomas
•>90% develop colorectal adenomas
•59 to 70% develop colorectal cancer
•58 to 70% develop high-grade brain tumours
•20-40% develop lymphoma
•10-40% develop leukemia
•10 to 18% develop small-bowel cancer
•<10% develop endometrial cancer
•<10% develop urinary tract cancer
•<10% develop cancer of other sites
BabyScreen+ newborn screening v0.1801 MLH1 Zornitza Stark Marked gene: MLH1 as ready
BabyScreen+ newborn screening v0.1801 MLH1 Zornitza Stark Gene: mlh1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1801 MLH1 Zornitza Stark Phenotypes for gene: MLH1 were changed from Lynch syndrome to Mismatch repair cancer syndrome 1, MIM# 276300
BabyScreen+ newborn screening v0.1800 MLH1 Zornitza Stark Mode of inheritance for gene: MLH1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1799 TMPRSS3 Seb Lunke Marked gene: TMPRSS3 as ready
BabyScreen+ newborn screening v0.1799 TMPRSS3 Seb Lunke Gene: tmprss3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1799 TMPRSS3 Seb Lunke Phenotypes for gene: TMPRSS3 were changed from Deafness, autosomal recessive to deafness, autosomal recessive MIM#601072
BabyScreen+ newborn screening v0.1798 TMPRSS3 Seb Lunke Publications for gene: TMPRSS3 were set to
BabyScreen+ newborn screening v0.1797 MSH2 Zornitza Stark Marked gene: MSH2 as ready
BabyScreen+ newborn screening v0.1797 MSH2 Zornitza Stark Gene: msh2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1797 MSH2 Zornitza Stark Phenotypes for gene: MSH2 were changed from Lynch syndrome to Mismatch repair cancer syndrome 2, MIM# 619096
BabyScreen+ newborn screening v0.1796 MLH1 Zornitza Stark Classified gene: MLH1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1796 MLH1 Zornitza Stark Gene: mlh1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1795 MSH2 Zornitza Stark Mode of inheritance for gene: MSH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1794 MSH2 Zornitza Stark Classified gene: MSH2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1794 MSH2 Zornitza Stark Gene: msh2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1793 MSH2 Zornitza Stark Tag for review tag was added to gene: MSH2.
Tag cancer tag was added to gene: MSH2.
Tag treatable tag was added to gene: MSH2.
BabyScreen+ newborn screening v0.1793 LYST Seb Lunke Marked gene: LYST as ready
BabyScreen+ newborn screening v0.1793 LYST Seb Lunke Gene: lyst has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1793 MSH2 Zornitza Stark reviewed gene: MSH2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mismatch repair cancer syndrome 2, MIM# 619096; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1793 COL9A2 Seb Lunke Marked gene: COL9A2 as ready
BabyScreen+ newborn screening v0.1793 COL9A2 Seb Lunke Gene: col9a2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1793 MLH1 Zornitza Stark Tag for review tag was added to gene: MLH1.
Tag cancer tag was added to gene: MLH1.
Tag treatable tag was added to gene: MLH1.
BabyScreen+ newborn screening v0.1793 MLH1 Zornitza Stark reviewed gene: MLH1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mismatch repair cancer syndrome 1, MIM# 276300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1793 TPRN Zornitza Stark Marked gene: TPRN as ready
BabyScreen+ newborn screening v0.1793 TPRN Zornitza Stark Gene: tprn has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1793 TPRN Zornitza Stark Phenotypes for gene: TPRN were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 79, MIM# 613307
BabyScreen+ newborn screening v0.1792 TPRN Zornitza Stark Classified gene: TPRN as Green List (high evidence)
BabyScreen+ newborn screening v0.1792 TPRN Zornitza Stark Gene: tprn has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1791 TPRN Zornitza Stark Tag deafness tag was added to gene: TPRN.
BabyScreen+ newborn screening v0.1791 TPRN Zornitza Stark reviewed gene: TPRN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 79, MIM# 613307; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1791 STRC Zornitza Stark Classified gene: STRC as Green List (high evidence)
BabyScreen+ newborn screening v0.1791 STRC Zornitza Stark Gene: strc has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1790 STRC Zornitza Stark Tag for review was removed from gene: STRC.
Tag deafness tag was added to gene: STRC.
BabyScreen+ newborn screening v0.1790 STRC Zornitza Stark reviewed gene: STRC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 16, MIM# 603720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1790 S1PR2 Zornitza Stark Marked gene: S1PR2 as ready
BabyScreen+ newborn screening v0.1790 S1PR2 Zornitza Stark Gene: s1pr2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1790 S1PR2 Zornitza Stark Classified gene: S1PR2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1790 S1PR2 Zornitza Stark Gene: s1pr2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1789 S1PR2 Zornitza Stark gene: S1PR2 was added
gene: S1PR2 was added to gNBS. Sources: ClinGen
deafness tags were added to gene: S1PR2.
Mode of inheritance for gene: S1PR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: S1PR2 were set to Deafness, autosomal recessive 68, MIM# 610419
Review for gene: S1PR2 was set to GREEN
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen, onset of deafness is generally pre-lingual, therefore include.
Sources: ClinGen
BabyScreen+ newborn screening v0.1788 PTPRQ Zornitza Stark Marked gene: PTPRQ as ready
BabyScreen+ newborn screening v0.1788 PTPRQ Zornitza Stark Gene: ptprq has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1788 PTPRQ Zornitza Stark Classified gene: PTPRQ as Green List (high evidence)
BabyScreen+ newborn screening v0.1788 PTPRQ Zornitza Stark Gene: ptprq has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1787 PTPRQ Zornitza Stark gene: PTPRQ was added
gene: PTPRQ was added to gNBS. Sources: ClinGen
deafness tags were added to gene: PTPRQ.
Mode of inheritance for gene: PTPRQ was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PTPRQ were set to Deafness, autosomal recessive 84A, MIM# 613391; Deafness, autosomal dominant 73, MIM# 617663
Review for gene: PTPRQ was set to GREEN
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen, onset of deafness is generally pre-lingual, therefore include.
Sources: ClinGen
BabyScreen+ newborn screening v0.1786 POU3F4 Zornitza Stark Classified gene: POU3F4 as Green List (high evidence)
BabyScreen+ newborn screening v0.1786 POU3F4 Zornitza Stark Gene: pou3f4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1785 POU3F4 Zornitza Stark Tag deafness tag was added to gene: POU3F4.
BabyScreen+ newborn screening v0.1785 POU3F4 Zornitza Stark Deleted their comment
BabyScreen+ newborn screening v0.1785 POU3F4 Zornitza Stark edited their review of gene: POU3F4: Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen, onset is generally pre-lingual, therefore include.; Changed rating: GREEN
BabyScreen+ newborn screening v0.1785 OTOG Zornitza Stark Marked gene: OTOG as ready
BabyScreen+ newborn screening v0.1785 OTOG Zornitza Stark Gene: otog has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1785 OTOG Zornitza Stark Phenotypes for gene: OTOG were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 18B - MIM#614945
BabyScreen+ newborn screening v0.1784 OTOG Zornitza Stark Classified gene: OTOG as Green List (high evidence)
BabyScreen+ newborn screening v0.1784 OTOG Zornitza Stark Gene: otog has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1783 OTOG Zornitza Stark Tag deafness tag was added to gene: OTOG.
BabyScreen+ newborn screening v0.1783 OTOG Zornitza Stark reviewed gene: OTOG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 18B - MIM#614945; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1783 MYO3A Zornitza Stark Classified gene: MYO3A as Green List (high evidence)
BabyScreen+ newborn screening v0.1783 MYO3A Zornitza Stark Gene: myo3a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1782 MYO3A Zornitza Stark Tag deafness tag was added to gene: MYO3A.
BabyScreen+ newborn screening v0.1782 MYO3A Zornitza Stark edited their review of gene: MYO3A: Added comment: Assessed by ClinGen as 'strong actionability' in paediatric patients.

Included as a cause of pre-lingual deafness, therefore include in this panel, noting some reports of later onset.; Changed rating: GREEN
BabyScreen+ newborn screening v0.1782 PRKG1 Zornitza Stark Marked gene: PRKG1 as ready
BabyScreen+ newborn screening v0.1782 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1782 PRKG1 Zornitza Stark Classified gene: PRKG1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1782 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1781 PRKG1 Zornitza Stark gene: PRKG1 was added
gene: PRKG1 was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: PRKG1.
Mode of inheritance for gene: PRKG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PRKG1 were set to Aortic aneurysm, familial thoracic 8, MIM#615436
Penetrance for gene: PRKG1 were set to Incomplete
Review for gene: PRKG1 was set to AMBER
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 31 individuals with PRKG1 pathogenic variants indicated that 63% presented with an aortic dissection and 37% had aortic root enlargement. The cumulative risk of an aortic dissection or repair of an aortic aneurysm by age 55 has been estimated as 86% (95% CI: 70-95%).
Sources: ClinGen
BabyScreen+ newborn screening v0.1780 MYH11 Zornitza Stark Marked gene: MYH11 as ready
BabyScreen+ newborn screening v0.1780 MYH11 Zornitza Stark Gene: myh11 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1780 MYH11 Zornitza Stark Phenotypes for gene: MYH11 were changed from Aortic aneurysm, familial thoracic 4 to Aortic aneurysm, familial thoracic 4, MIM#160745
BabyScreen+ newborn screening v0.1779 MYH11 Zornitza Stark Tag for review tag was added to gene: MYH11.
Tag cardiac tag was added to gene: MYH11.
Tag treatable tag was added to gene: MYH11.
BabyScreen+ newborn screening v0.1779 MYH11 Zornitza Stark reviewed gene: MYH11: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aortic aneurysm, familial thoracic 4, MIM#160745; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1779 LOX Zornitza Stark Marked gene: LOX as ready
BabyScreen+ newborn screening v0.1779 LOX Zornitza Stark Gene: lox has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1779 LOX Zornitza Stark Classified gene: LOX as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1779 LOX Zornitza Stark Gene: lox has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1778 LOX Zornitza Stark gene: LOX was added
gene: LOX was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: LOX.
Mode of inheritance for gene: LOX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LOX were set to Aortic aneurysm, familial thoracic 10, MIM#617168
Penetrance for gene: LOX were set to Incomplete
Review for gene: LOX was set to AMBER
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection.
Sources: ClinGen
BabyScreen+ newborn screening v0.1777 ACTA2 Zornitza Stark Marked gene: ACTA2 as ready
BabyScreen+ newborn screening v0.1777 ACTA2 Zornitza Stark Gene: acta2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1777 ACTA2 Zornitza Stark Phenotypes for gene: ACTA2 were changed from Aortic aneurysm, familial thoracic to Aortic aneurysm, familial thoracic 6, MIM# 611788
BabyScreen+ newborn screening v0.1776 ACTA2 Zornitza Stark Tag for review tag was added to gene: ACTA2.
Tag cardiac tag was added to gene: ACTA2.
Tag treatable tag was added to gene: ACTA2.
BabyScreen+ newborn screening v0.1776 ACTA2 Zornitza Stark reviewed gene: ACTA2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aortic aneurysm, familial thoracic 6, MIM# 611788; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1776 STK11 Zornitza Stark Classified gene: STK11 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1776 STK11 Zornitza Stark Gene: stk11 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1775 STK11 Zornitza Stark Tag cancer tag was added to gene: STK11.
Tag treatable tag was added to gene: STK11.
BabyScreen+ newborn screening v0.1775 STK11 Zornitza Stark reviewed gene: STK11: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Peutz-Jeghers syndrome, MIM# 175200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1775 MCEE Zornitza Stark Marked gene: MCEE as ready
BabyScreen+ newborn screening v0.1775 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1775 MCEE Zornitza Stark Phenotypes for gene: MCEE were changed from Methylmalonyl-CoA epimerase deficiency to Methylmalonyl-CoA epimerase deficiency MIM#251120
BabyScreen+ newborn screening v0.1774 MCEE Zornitza Stark Classified gene: MCEE as Green List (high evidence)
BabyScreen+ newborn screening v0.1774 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1773 MCEE Zornitza Stark Tag for review tag was added to gene: MCEE.
Tag treatable tag was added to gene: MCEE.
Tag metabolic tag was added to gene: MCEE.
BabyScreen+ newborn screening v0.1773 MCEE Zornitza Stark reviewed gene: MCEE: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Methylmalonyl-CoA epimerase deficiency MIM#251120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1773 RUNX1 Zornitza Stark Marked gene: RUNX1 as ready
BabyScreen+ newborn screening v0.1773 RUNX1 Zornitza Stark Gene: runx1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1773 RUNX1 Zornitza Stark Classified gene: RUNX1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1773 RUNX1 Zornitza Stark Gene: runx1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1772 RUNX1 Zornitza Stark gene: RUNX1 was added
gene: RUNX1 was added to gNBS. Sources: ClinGen
for review, treatable, haematological tags were added to gene: RUNX1.
Mode of inheritance for gene: RUNX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RUNX1 were set to Platelet disorder, familial, with associated myeloid malignancy, MIM# 601399
Review for gene: RUNX1 was set to AMBER
Added comment: Assessed as 'moderate actionability' in paediatric patients by ClinGen.

HTHCPS is characterized by mild to moderate thrombocytopenia with normal platelet size, abnormal platelet functioning (defective release of delta granules and/or aggregation defects), and an increased risk of developing a haematologic malignancy.

Age of onset of bleeding can be highly variable, with some individuals presenting in early infancy and others not recognizing their symptoms until much later in life. Severe thrombocytopenia or profound platelet dysfunction can result in recognition during the perinatal or infancy period. Hematologic malignancies can occur in childhood or adulthood; the range of age of onset is wide with a median age of 33 years.

Use of clotting promotors (e.g., desmopressin, epsilon aminocaproic acid, tranexamic acid) can be used for surgeries, injuries, or dental treatments. Platelet transfusions may be used for severe bleeding or procedures with a high bleeding risk.

Though there is no specific treatment for HTHCPS, there are recommendations regarding the indications and timing of hematopoietic stem cell transplantation (HSCT) that vary. HSCT in pre-malignancy patients, particularly in the absence of any clonal progression, is debatable due to transplantation-associated risks and incomplete penetrance. Some suggested indications for HSCT include severe or symptomatic cytopenias, severe marrow dysplasia (particularly in the context of falling blood counts), complex or high-risk (e.g., monosomy 7) cytogenetic abnormalities (particularly if the clones are large or increasing in size) and increasing blasts >5%.

Consider use of a medical alert bracelet for thrombocytopenia, platelet dysfunction, or hematologic malignancy as indicated.
Sources: ClinGen
BabyScreen+ newborn screening v0.1771 DICER1 Zornitza Stark Marked gene: DICER1 as ready
BabyScreen+ newborn screening v0.1771 DICER1 Zornitza Stark Gene: dicer1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1771 DICER1 Zornitza Stark Classified gene: DICER1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1771 DICER1 Zornitza Stark Gene: dicer1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1770 DICER1 Zornitza Stark Tag for review tag was added to gene: DICER1.
Tag cancer tag was added to gene: DICER1.
Tag treatable tag was added to gene: DICER1.
BabyScreen+ newborn screening v0.1770 DICER1 Zornitza Stark gene: DICER1 was added
gene: DICER1 was added to gNBS. Sources: ClinGen
Mode of inheritance for gene: DICER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DICER1 were set to DICER1 syndrome, MONDO:0017288
Penetrance for gene: DICER1 were set to Incomplete
Review for gene: DICER1 was set to AMBER
Added comment: Rated as 'moderate actionability' in paediatric patients by ClinGen.

A multiple registry study examining neoplasm incidence in a cohort containing 102 non-probands with DICER1 pathogenic variants (3,344 person-years of observation in non-probands) found that by age 10 years, 5.3% (95% CI, 0.6% to 9.7%) of non-probands had developed a neoplasm (females, 4.0%; males, 6.6%). By age 50 years, 19.3% (95% CI, 8.4% to 29.0%) of non-probands had developed a neoplasm (females, 26.5%; males, 10.2%).

Most individuals with pathogenic variants in DICER1 are healthy or have only minor DICER1-associaited conditions. The most severe manifestations tend to present in early childhood with adulthood characterized by good health. The majority of tumors in individuals with DICER1 pathogenic variants occur in individuals younger than 40. Many of these tumors typically only occur in childhood, including: PPB (before age 7), CN (before age 4), CBME typically occurs in young children, pituitary blastoma (before age 2), and childhood pineoblastoma (only one has been reported associated with a DICER1 mutation).

Surveillance recommendations:
In order to detect pulmonary cysts or PPB (one of the most important causes of DICER1-associated morbidity and mortality), chest x-rays are recommended every 6 months from birth to through age 7 years and then annually from 8-12 years. A chest computed tomography (CT) (with efforts to minimize radiation) should be obtained by 9 months of age, preferably between 3 and 6 months of age and repeated at approximately 2.5 years of age.

Abdominal ultrasound is recommended for the detection in infancy or at the time of the first chest CT then every 6-12 months until at least 8 years of age. Annual ultrasound may be considered until 12 years of age.

Beginning at ages 8-10 females should receive pelvic ultrasound performed in conjunction with abdominal ultrasound (every 6-12 months) until at least age 40 or as needed for signs and symptoms.

Individuals should undergo thyroid ultrasound with assessment for regional adenopathy every 2 to 3 years starting at age 8 or as needed for signs and symptoms.

An annual routine dilated ophthalmologic exam with visual acuity screening is recommended from age 3 to at least age 10 for detection of CBME.
Sources: ClinGen
BabyScreen+ newborn screening v0.1769 BRCA1 Zornitza Stark Marked gene: BRCA1 as ready
BabyScreen+ newborn screening v0.1769 BRCA1 Zornitza Stark Gene: brca1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1769 BRCA1 Zornitza Stark Phenotypes for gene: BRCA1 were changed from Breast-ovarian cancer, familial, 1 to Fanconi anemia, complementation group S, MIM# 617883
BabyScreen+ newborn screening v0.1768 BRCA1 Zornitza Stark Mode of inheritance for gene: BRCA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1767 BRCA1 Zornitza Stark Classified gene: BRCA1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1767 BRCA1 Zornitza Stark Gene: brca1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1766 BRCA1 Zornitza Stark Tag treatable tag was added to gene: BRCA1.
Tag haematological tag was added to gene: BRCA1.
BabyScreen+ newborn screening v0.1766 BRCA1 Zornitza Stark reviewed gene: BRCA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group S, MIM# 617883; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1766 BRCA2 Zornitza Stark Marked gene: BRCA2 as ready
BabyScreen+ newborn screening v0.1766 BRCA2 Zornitza Stark Gene: brca2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1766 BRCA2 Zornitza Stark Phenotypes for gene: BRCA2 were changed from Fanconi anaemia, complementation group D, MIM#1 605724; Fanconi anemia, complementation group D1; Breast-ovarian cancer, familial, 2 to Fanconi anaemia, complementation group D1, MIM# 605724
BabyScreen+ newborn screening v0.1765 BRCA2 Zornitza Stark Mode of inheritance for gene: BRCA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1764 BRCA2 Zornitza Stark Classified gene: BRCA2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1764 BRCA2 Zornitza Stark Gene: brca2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1763 BRCA2 Zornitza Stark Tag treatable tag was added to gene: BRCA2.
Tag haematological tag was added to gene: BRCA2.
BabyScreen+ newborn screening v0.1763 BRCA2 Zornitza Stark reviewed gene: BRCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group D1, MIM# 605724; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1763 KCNQ1 Zornitza Stark Marked gene: KCNQ1 as ready
BabyScreen+ newborn screening v0.1763 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1763 KCNQ1 Zornitza Stark Phenotypes for gene: KCNQ1 were changed from Short QT syndrome 2, MIM# 609621; Jervell and Lange-Nielsen syndrome; Long QT syndrome 1, MIM# 192500; Long QT syndrome-1; Jervell and Lange-Nielsen syndrome, MIM# 220400 to Long QT syndrome 1, MIM# 192500
BabyScreen+ newborn screening v0.1762 KCNQ1 Zornitza Stark Tag for review tag was added to gene: KCNQ1.
Tag cardiac tag was added to gene: KCNQ1.
Tag treatable tag was added to gene: KCNQ1.
BabyScreen+ newborn screening v0.1762 KCNQ1 Zornitza Stark reviewed gene: KCNQ1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Long QT syndrome 1, MIM# 192500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1762 KCNH2 Zornitza Stark Marked gene: KCNH2 as ready
BabyScreen+ newborn screening v0.1762 KCNH2 Zornitza Stark Gene: kcnh2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1762 KCNH2 Zornitza Stark Phenotypes for gene: KCNH2 were changed from Long QT syndrome-2 to Long QT syndrome 2, MIM# 613688
BabyScreen+ newborn screening v0.1761 KCNH2 Zornitza Stark Tag for review tag was added to gene: KCNH2.
Tag cardiac tag was added to gene: KCNH2.
Tag treatable tag was added to gene: KCNH2.
BabyScreen+ newborn screening v0.1761 KCNH2 Zornitza Stark reviewed gene: KCNH2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Long QT syndrome 2, MIM# 613688; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1761 TMEM43 Zornitza Stark Tag for review tag was added to gene: TMEM43.
Tag cardiac tag was added to gene: TMEM43.
Tag treatable tag was added to gene: TMEM43.
BabyScreen+ newborn screening v0.1761 TMEM43 Zornitza Stark reviewed gene: TMEM43: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 5 MIM#604400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1761 PKP2 Zornitza Stark Marked gene: PKP2 as ready
BabyScreen+ newborn screening v0.1761 PKP2 Zornitza Stark Gene: pkp2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1761 PKP2 Zornitza Stark Phenotypes for gene: PKP2 were changed from Arrhythmogenic right ventricular dysplasia 9 to Arrhythmogenic right ventricular dysplasia 9, MIM# 609040
BabyScreen+ newborn screening v0.1760 PKP2 Zornitza Stark Tag for review tag was added to gene: PKP2.
Tag cardiac tag was added to gene: PKP2.
Tag treatable tag was added to gene: PKP2.
BabyScreen+ newborn screening v0.1760 PKP2 Zornitza Stark reviewed gene: PKP2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 9, MIM# 609040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1760 DSP Zornitza Stark Marked gene: DSP as ready
BabyScreen+ newborn screening v0.1760 DSP Zornitza Stark Gene: dsp has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1760 DSP Zornitza Stark Phenotypes for gene: DSP were changed from Cardiomyopathy, dilated, with woolly hair and keratoderma, MIM# 605676; Epidermolysis bullosa, lethal acantholytic; Arrhythmogenic right ventricular dysplasia/cardiomyopathy; Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis , MIM#615821 to Arrhythmogenic right ventricular dysplasia 8, MIM# 607450
BabyScreen+ newborn screening v0.1759 DSP Zornitza Stark Mode of inheritance for gene: DSP was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1758 DSP Zornitza Stark Tag for review tag was added to gene: DSP.
Tag cardiac tag was added to gene: DSP.
Tag treatable tag was added to gene: DSP.
BabyScreen+ newborn screening v0.1758 DSP Zornitza Stark reviewed gene: DSP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 8, MIM# 607450; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1758 DSG2 Zornitza Stark Marked gene: DSG2 as ready
BabyScreen+ newborn screening v0.1758 DSG2 Zornitza Stark Gene: dsg2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1758 DSG2 Zornitza Stark Phenotypes for gene: DSG2 were changed from Arrhythmogenic right ventricular cardiomyopathy to Arrhythmogenic right ventricular dysplasia 10, MIM# 610193
BabyScreen+ newborn screening v0.1757 DSG2 Zornitza Stark Tag for review tag was added to gene: DSG2.
Tag cardiac tag was added to gene: DSG2.
Tag treatable tag was added to gene: DSG2.
BabyScreen+ newborn screening v0.1757 DSG2 Zornitza Stark reviewed gene: DSG2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 10, MIM# 610193; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1757 JUP Zornitza Stark Marked gene: JUP as ready
BabyScreen+ newborn screening v0.1757 JUP Zornitza Stark Gene: jup has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1757 JUP Zornitza Stark Phenotypes for gene: JUP were changed from Arrhythmogenic right ventricular dysplasia 12; Naxos disease to Arrhythmogenic right ventricular dysplasia 12 MIM# 611528; Naxos disease MIM# 601214
BabyScreen+ newborn screening v0.1756 JUP Zornitza Stark Tag for review tag was added to gene: JUP.
Tag cardiac tag was added to gene: JUP.
Tag treatable tag was added to gene: JUP.
BabyScreen+ newborn screening v0.1756 JUP Zornitza Stark reviewed gene: JUP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 12 MIM# 611528, Naxos disease MIM# 601214; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1756 DSC2 Zornitza Stark Marked gene: DSC2 as ready
BabyScreen+ newborn screening v0.1756 DSC2 Zornitza Stark Gene: dsc2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1756 DSC2 Zornitza Stark Phenotypes for gene: DSC2 were changed from Arrhythmogenic right ventricular cardiomyopathy to Arrhythmogenic right ventricular dysplasia 11, MIM# 610476; Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476
BabyScreen+ newborn screening v0.1755 DSC2 Zornitza Stark Mode of inheritance for gene: DSC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1754 DSC2 Zornitza Stark Tag for review tag was added to gene: DSC2.
Tag cardiac tag was added to gene: DSC2.
Tag treatable tag was added to gene: DSC2.
BabyScreen+ newborn screening v0.1754 DSC2 Zornitza Stark edited their review of gene: DSC2: Changed rating: AMBER
BabyScreen+ newborn screening v0.1754 DSC2 Zornitza Stark reviewed gene: DSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 11, MIM# 610476, Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1754 OAT Zornitza Stark Marked gene: OAT as ready
BabyScreen+ newborn screening v0.1754 OAT Zornitza Stark Gene: oat has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1754 OAT Zornitza Stark Classified gene: OAT as Green List (high evidence)
BabyScreen+ newborn screening v0.1754 OAT Zornitza Stark Gene: oat has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1753 OAT Zornitza Stark gene: OAT was added
gene: OAT was added to gNBS. Sources: ClinGen
for review, treatable, metabolic tags were added to gene: OAT.
Mode of inheritance for gene: OAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OAT were set to Gyrate atrophy of choroid and retina with or without ornithinemia MIM#258870
Review for gene: OAT was set to GREEN
Added comment: Rated as 'moderate actionability' in paediatric patients by ClinGen.

GA due to deficiency of the enzyme ornithine aminotransferase (OAT) is characterized by a triad of progressive chorioretinal degeneration, early cataract formation, and type II muscle fiber atrophy. GA first presents as night blindness and constriction of the visual field caused by sharply demarcated circular areas of chorioretinal atrophy in the periphery. Atrophic areas progressively increase, coalesce, and spread towards the macula leading to central visual loss and blindness (vision less than 20/200).

Age at diagnosis ranges from 1 month to 44 years. The condition is characterized by the development of chorioretinal atrophic patches that start in the mid-peripheral retina in the first decade of life. Myopia, night blindness, changes in the macula (including cystic changes), and visual field affection usually start in the first or second decade. Most patients with GA have posterior subcapsular cataracts by the end of the second decade. Irreversible loss of vision and blindness generally occurs between 40 and 55 years of age but is highly variable.

Treatment of GA consists mainly of dietary modifications to help lower elevated systemic ornithine levels. Restriction of dietary arginine, a precursor of ornithine, appears to have therapeutic value. Pediatric patients undergoing arginine restriction should receive enough calories in their diet supplemented by essential amino acids, vitamins, and minerals to avoid malnutrition and excessive break down of endogenous proteins.

A long-term observational study of 27 patients with GA, 17 who complied with the arginine-restricted diet and 10 who were noncompliant, found that at 14 years follow-up the rates of vision loss were significantly slower in the compliant group for 3 of the 4 outcome measures, when adjusted for age.
Sources: ClinGen
BabyScreen+ newborn screening v0.1752 PCSK9 Zornitza Stark Marked gene: PCSK9 as ready
BabyScreen+ newborn screening v0.1752 PCSK9 Zornitza Stark Gene: pcsk9 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1752 PCSK9 Zornitza Stark Phenotypes for gene: PCSK9 were changed from Hypercholesterolemia to Hypercholesterolaemia, familial, 3, MIM# 603776
BabyScreen+ newborn screening v0.1751 PCSK9 Zornitza Stark Classified gene: PCSK9 as Green List (high evidence)
BabyScreen+ newborn screening v0.1751 PCSK9 Zornitza Stark Gene: pcsk9 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1750 PCSK9 Zornitza Stark Tag for review tag was added to gene: PCSK9.
Tag treatable tag was added to gene: PCSK9.
Tag metabolic tag was added to gene: PCSK9.
BabyScreen+ newborn screening v0.1750 PCSK9 Zornitza Stark reviewed gene: PCSK9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypercholesterolemia, familial, 3, MIM# 603776; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1750 PRKAR1A Zornitza Stark Phenotypes for gene: PRKAR1A were changed from Acrodysostosis 1, with or without hormone resistance, MIM# 101800; Carney complex, type 1, MIM# 160980; Myxoma, intracardiac, MIM# 255960; Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489 to Carney complex, type 1, MIM# 160980
BabyScreen+ newborn screening v0.1749 PRKAR1A Zornitza Stark Classified gene: PRKAR1A as Green List (high evidence)
BabyScreen+ newborn screening v0.1749 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1748 PRKAR1A Zornitza Stark Tag for review tag was added to gene: PRKAR1A.
Tag cancer tag was added to gene: PRKAR1A.
Tag treatable tag was added to gene: PRKAR1A.
BabyScreen+ newborn screening v0.1748 PRKAR1A Zornitza Stark Deleted their comment
BabyScreen+ newborn screening v0.1748 PRKAR1A Zornitza Stark edited their review of gene: PRKAR1A: Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen, principally due to benefit from early detection of cardiac myxomas through surveillance.

CNC is associated with skin pigmentary abnormalities, myxomas, endocrine tumors or overactivity, and schwannomas.

Lentigines are the most common presenting feature of CNC and may be present at birth. Typically, they increase in number at puberty, fade after the fourth decade, but may still be evident in the eighth decade. Cutaneous myxomas appear between birth and the fourth decade. Cardiac myxomas may occur at a young age. Breast myxomas occur in females after puberty. Males and females may develop nipple myxomas at any age. In a minority of individuals, PPNAD presents in the first two to three years; in the majority, it presents in the second or third decade. LCCSCT often present in the first decade. Signs and symptoms of CNC may be present at birth, but the median age of diagnosis is 20 years. Most patients with CNC present with a mild increase in GH. However, clinically evident acromegaly is a relatively frequent manifestation of CNC, occurring in approximately 10% of adults at the time of presentation. Most individuals with CNC have a normal life span. However, because some die at an early age, the average life expectancy for individuals with CNC is 50 years. Causes of death include complications of cardiac myxoma (myxoma emboli, cardiomyopathy, cardiac arrhythmia, and surgical intervention), metastatic or intracranial PMS, thyroid carcinoma, and metastatic pancreatic and testicular tumors.

The only preventive measure in an asymptomatic individual is surgical removal of a heart tumor (cardiac myxoma) prior to the development of heart dysfunction, stroke, or other embolism. Cardiac myxomas should be diagnosed early through regular screening.

Development of metabolic abnormalities from Cushing syndrome or arthropathy and other complications from acromegaly may be prevented by medical or surgical treatment of the respective endocrine manifestations.

The overall penetrance of CNC in those with a PRKAR1A pathogenic variant is greater than 95% by age 50 years. 30-60% have cardiac myxomas.; Changed rating: GREEN; Changed phenotypes: Carney complex, type 1, MIM# 160980
BabyScreen+ newborn screening v0.1748 RPS10 Zornitza Stark Marked gene: RPS10 as ready
BabyScreen+ newborn screening v0.1748 RPS10 Zornitza Stark Gene: rps10 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1748 RPS10 Zornitza Stark Phenotypes for gene: RPS10 were changed from Diamond-Blackfan anaemia 9, MIM# 613308; Diamond-Blackfan anemia to Diamond-Blackfan anaemia 9, MIM# 613308
BabyScreen+ newborn screening v0.1747 RPS10 Zornitza Stark Classified gene: RPS10 as Green List (high evidence)
BabyScreen+ newborn screening v0.1747 RPS10 Zornitza Stark Gene: rps10 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1746 RPS10 Zornitza Stark Tag treatable tag was added to gene: RPS10.
Tag haematological tag was added to gene: RPS10.
BabyScreen+ newborn screening v0.1746 RPS10 Zornitza Stark reviewed gene: RPS10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diamond-Blackfan anaemia 9, MIM# 613308; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1746 MEN1 Zornitza Stark Tag treatable tag was added to gene: MEN1.
BabyScreen+ newborn screening v0.1746 MEN1 Zornitza Stark changed review comment from: For review re age of onset: surveillance starts age 5, disease onset generally later.; to: For review re age of onset: surveillance starts age 5, disease onset generally later.

Rated as 'strong actionability' in paediatric patients by ClinGen.

Parathyroid tumors, which cause PHPT, are the most common feature and the first clinical manifestation in 90% of individuals with MEN1 with onset typically between ages 20 and 25 years. Almost all (95-100%) individuals with MEN1 can expect to have PHPT by age 50 years. However, MEN1 affects all age groups, with a reported age range of 5 to 81 years; 17% of MEN1 tumors are diagnosed under age 21. Untreated patients with MEN1 have a decreased life expectancy with a 50% probability of death by age 50. The cause of death in 50-70% of cases is due to a malignant tumor process or sequelae of the disease, with malignancies accounting for 30% of all deaths.
BabyScreen+ newborn screening v0.1746 MEN1 Zornitza Stark Tag for review tag was added to gene: MEN1.
Tag cancer tag was added to gene: MEN1.
BabyScreen+ newborn screening v0.1746 SCN5A Zornitza Stark Marked gene: SCN5A as ready
BabyScreen+ newborn screening v0.1746 SCN5A Zornitza Stark Gene: scn5a has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1746 SCN5A Zornitza Stark Phenotypes for gene: SCN5A were changed from Sick sinus syndrome 1, MIM# 608567; Ventricular fibrillation, familial, 1, MIM# 603829; Brugada syndrome; Brugada syndrome 1, MIM# 601144; Long QT syndrome 3 (MIM#603830); Long QT syndrome; Heart block, progressive, type IA, MIM# 113900 to Long QT syndrome 3 (MIM#603830); Brugada syndrome 1, MIM# 601144
BabyScreen+ newborn screening v0.1745 SCN5A Zornitza Stark Tag for review tag was added to gene: SCN5A.
Tag cardiac tag was added to gene: SCN5A.
Tag treatable tag was added to gene: SCN5A.
BabyScreen+ newborn screening v0.1745 SCN5A Zornitza Stark reviewed gene: SCN5A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Long QT syndrome 3 (MIM#603830), Brugada syndrome 1, MIM# 601144; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1745 SLC26A4 Zornitza Stark Phenotypes for gene: SLC26A4 were changed from Pendred syndrome, MIM #274600 to Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791; Pendred syndrome 274600
BabyScreen+ newborn screening v0.1744 SLC26A4 Zornitza Stark Classified gene: SLC26A4 as Green List (high evidence)
BabyScreen+ newborn screening v0.1744 SLC26A4 Zornitza Stark Gene: slc26a4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1743 SLC26A4 Zornitza Stark Tag for review was removed from gene: SLC26A4.
Tag deafness tag was added to gene: SLC26A4.
BabyScreen+ newborn screening v0.1743 SLC26A4 Zornitza Stark reviewed gene: SLC26A4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791, Pendred syndrome 274600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1743 TGFB3 Zornitza Stark Marked gene: TGFB3 as ready
BabyScreen+ newborn screening v0.1743 TGFB3 Zornitza Stark Gene: tgfb3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1743 TGFB3 Zornitza Stark Phenotypes for gene: TGFB3 were changed from Arrhythmogenic right ventricular dysplasia to Loeys-Dietz syndrome 5 , MIM#615582
BabyScreen+ newborn screening v0.1742 TGFB3 Zornitza Stark Classified gene: TGFB3 as Green List (high evidence)
BabyScreen+ newborn screening v0.1742 TGFB3 Zornitza Stark Gene: tgfb3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1741 TGFB3 Zornitza Stark Tag for review tag was added to gene: TGFB3.
Tag cardiac tag was added to gene: TGFB3.
Tag treatable tag was added to gene: TGFB3.
BabyScreen+ newborn screening v0.1741 TGFB3 Zornitza Stark reviewed gene: TGFB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 5 , MIM#615582; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1741 TGFB2 Zornitza Stark Marked gene: TGFB2 as ready
BabyScreen+ newborn screening v0.1741 TGFB2 Zornitza Stark Gene: tgfb2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1741 TGFB2 Zornitza Stark Classified gene: TGFB2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1741 TGFB2 Zornitza Stark Gene: tgfb2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1740 TGFB2 Zornitza Stark Tag for review tag was added to gene: TGFB2.
Tag cardiac tag was added to gene: TGFB2.
Tag treatable tag was added to gene: TGFB2.
BabyScreen+ newborn screening v0.1740 TGFB2 Zornitza Stark gene: TGFB2 was added
gene: TGFB2 was added to gNBS. Sources: ClinGen
Mode of inheritance for gene: TGFB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TGFB2 were set to Loeys-Dietz syndrome 4, MIM# 614816
Review for gene: TGFB2 was set to GREEN
Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen.

Individuals with LDS are predisposed to widespread and aggressive arterial aneurysms which are the major source of morbidity and mortality. Aortic growth can be faster than 10mm per year. Aortic dissection has been observed in early childhood, and the mean age of death is 26 years. Other life-threatening manifestations include spontaneous rupture of the spleen, bowel, and uterine rupture during pregnancy.

Prophylactic surgical repair is typically recommended at an aortic diameter of ≥ 4.2 cm.

Beta-blockers or other medications can be used to reduce hemodynamic stress.

Consider Medicalert bracelet.

Use of subacute bacterial endocarditis prophylaxis should be considered for individuals with connective tissue disorders and documented evidence of mitral and/or aortic regurgitation who are undergoing dental work or other procedures expected to contaminate the bloodstream with bacteria.

Because of a high risk of cervical spine instability, a flexion and extension x-ray of the cervical spine should be performed prior to intubation or any other procedure involving manipulation of the neck.
Sources: ClinGen
BabyScreen+ newborn screening v0.1739 TRDN Zornitza Stark Marked gene: TRDN as ready
BabyScreen+ newborn screening v0.1739 TRDN Zornitza Stark Gene: trdn has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1739 TRDN Zornitza Stark Phenotypes for gene: TRDN were changed from Catecholaminergic polymorphic ventricular tachycardia to Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, MIM# 615441
BabyScreen+ newborn screening v0.1738 TRDN Zornitza Stark Classified gene: TRDN as Green List (high evidence)
BabyScreen+ newborn screening v0.1738 TRDN Zornitza Stark Gene: trdn has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1737 TRDN Zornitza Stark Tag for review tag was added to gene: TRDN.
Tag cardiac tag was added to gene: TRDN.
Tag treatable tag was added to gene: TRDN.
BabyScreen+ newborn screening v0.1737 TRDN Zornitza Stark reviewed gene: TRDN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, MIM# 615441; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1737 TECRL Zornitza Stark Marked gene: TECRL as ready
BabyScreen+ newborn screening v0.1737 TECRL Zornitza Stark Gene: tecrl has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1737 TECRL Zornitza Stark Classified gene: TECRL as Green List (high evidence)
BabyScreen+ newborn screening v0.1737 TECRL Zornitza Stark Gene: tecrl has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1736 TECRL Zornitza Stark gene: TECRL was added
gene: TECRL was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: TECRL.
Mode of inheritance for gene: TECRL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TECRL were set to Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021
Review for gene: TECRL was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen
BabyScreen+ newborn screening v0.1735 CALM3 Zornitza Stark Marked gene: CALM3 as ready
BabyScreen+ newborn screening v0.1735 CALM3 Zornitza Stark Gene: calm3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1735 CALM3 Zornitza Stark Classified gene: CALM3 as Green List (high evidence)
BabyScreen+ newborn screening v0.1735 CALM3 Zornitza Stark Gene: calm3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1734 CALM3 Zornitza Stark gene: CALM3 was added
gene: CALM3 was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: CALM3.
Mode of inheritance for gene: CALM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CALM3 were set to Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM# 618782
Penetrance for gene: CALM3 were set to Incomplete
Review for gene: CALM3 was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen
BabyScreen+ newborn screening v0.1733 CALM2 Zornitza Stark Marked gene: CALM2 as ready
BabyScreen+ newborn screening v0.1733 CALM2 Zornitza Stark Gene: calm2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1733 CALM2 Zornitza Stark Classified gene: CALM2 as Green List (high evidence)
BabyScreen+ newborn screening v0.1733 CALM2 Zornitza Stark Gene: calm2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1732 CALM2 Zornitza Stark gene: CALM2 was added
gene: CALM2 was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: CALM2.
Mode of inheritance for gene: CALM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CALM2 were set to Catecholaminergic polymorphic ventricular tachycardia MONDO:0017990
Review for gene: CALM2 was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen
BabyScreen+ newborn screening v0.1731 CALM1 Zornitza Stark Marked gene: CALM1 as ready
BabyScreen+ newborn screening v0.1731 CALM1 Zornitza Stark Gene: calm1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1731 CALM1 Zornitza Stark Classified gene: CALM1 as Green List (high evidence)
BabyScreen+ newborn screening v0.1731 CALM1 Zornitza Stark Gene: calm1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1730 CALM1 Zornitza Stark gene: CALM1 was added
gene: CALM1 was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: CALM1.
Mode of inheritance for gene: CALM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CALM1 were set to Ventricular tachycardia, catecholaminergic polymorphic, 4, MIM# 614916
Penetrance for gene: CALM1 were set to Incomplete
Review for gene: CALM1 was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen
BabyScreen+ newborn screening v0.1729 RPE65 Zornitza Stark Marked gene: RPE65 as ready
BabyScreen+ newborn screening v0.1729 RPE65 Zornitza Stark Gene: rpe65 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1729 RPE65 Zornitza Stark Classified gene: RPE65 as Green List (high evidence)
BabyScreen+ newborn screening v0.1729 RPE65 Zornitza Stark Gene: rpe65 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1728 RPE65 Zornitza Stark gene: RPE65 was added
gene: RPE65 was added to gNBS. Sources: ClinGen
for review, treatable, ophthalmological tags were added to gene: RPE65.
Mode of inheritance for gene: RPE65 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RPE65 were set to Leber congenital amaurosis 2 MIM#204100; Retinitis pigmentosa 20 MIM#613794
Review for gene: RPE65 was set to GREEN
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen.

Biallelic RPE65 mutation-associated retinal dystrophy is a form of IRD caused by biallelic pathogenic variants in RPE65; it presents as a spectrum of disease with variable age of onset and progression of vision loss. Common clinical findings across the spectrum include night blindness, progressive loss of visual fields and loss of central vision.

In LCA, night blindness often occurs from birth. Characteristically, these patients have residual cone-mediated vision in the first to third decades with progressive visual field loss until complete blindness is observed, most often in mid- to late-adulthood. A range of age of onset has been described for night blindness in RP, but it typically onsets in later childhood.

In December 2017, the FDA approved LUXTURNA (voretigene neparvovec-rzyl) gene therapy for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. The FDA’s conclusion of efficacy is based on improvement in a functional vision score over 1 year in a single open-label controlled Phase 3 study of 31 affected patients. The average age of the 31 randomized patients was 15 years (range 4 to 44 years), including 64% pediatric subjects (n=20, age from 4 to 17 years) and 36% adults (n=11). Functional vision was scored by a patient’s ability to navigate a course in various luminance levels. Using both treated eyes of the 21 subjects in the LUXTURNA treatment group, 11 (52%) had a clinically meaningful score improvement, while only one of the ten (10%) subjects in the control group had a clinically meaningful score improvement. Using the first treated eye only, 15/21 (71%) had a clinically meaningful score improvement, while no comparable score improvement was observed in controls. Other secondary clinical outcomes were also examined. Analysis of white light full-field light sensitivity threshold testing showed statistically significant improvement at 1 year in the LUXTURNA treatment group compared to the control group. The change in visual acuity was not significantly different between the LUXTURNA and control groups.

LUXTURNA is administered subretinally by injection. Per the FDA package insert, the most common adverse reactions (incidence ≥ 5%) in the clinical trials for LUXTURNA included conjunctival hyperemia, cataract, increased intraocular pressure, retinal tear, dellen (thinning of the corneal stroma), and macular hole. Several other ocular adverse effects were also reported, including risk of endophthalmitis. Safety data was included on the basis of 41 patients (81 eyes).

For review: availability of therapy?
Sources: ClinGen
BabyScreen+ newborn screening v0.1727 CP Zornitza Stark Marked gene: CP as ready
BabyScreen+ newborn screening v0.1727 CP Zornitza Stark Gene: cp has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1727 CP Zornitza Stark Phenotypes for gene: CP were changed from Aceruloplasminaemia to Aceruloplasminaemia, MIM#604290
BabyScreen+ newborn screening v0.1726 CP Zornitza Stark Tag treatable tag was added to gene: CP.
Tag metabolic tag was added to gene: CP.
BabyScreen+ newborn screening v0.1726 CP Zornitza Stark reviewed gene: CP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aceruloplasminaemia, MIM#604290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1726 WT1 Zornitza Stark Marked gene: WT1 as ready
BabyScreen+ newborn screening v0.1726 WT1 Zornitza Stark Gene: wt1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1726 WT1 Zornitza Stark Phenotypes for gene: WT1 were changed from Denys-Drash syndrome; Wilms tumor, type 1; Frasier syndrome to Wilms tumor, type 1, MIM#194070
BabyScreen+ newborn screening v0.1725 WT1 Zornitza Stark Tag for review tag was added to gene: WT1.
Tag cancer tag was added to gene: WT1.
Tag treatable tag was added to gene: WT1.
BabyScreen+ newborn screening v0.1725 WT1 Zornitza Stark reviewed gene: WT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Wilms tumor, type 1, MIM#194070; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1725 ITGB3 Zornitza Stark Marked gene: ITGB3 as ready
BabyScreen+ newborn screening v0.1725 ITGB3 Zornitza Stark Gene: itgb3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1725 ITGB3 Zornitza Stark Classified gene: ITGB3 as Green List (high evidence)
BabyScreen+ newborn screening v0.1725 ITGB3 Zornitza Stark Gene: itgb3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1724 ITGB3 Zornitza Stark gene: ITGB3 was added
gene: ITGB3 was added to gNBS. Sources: ClinGen
treatable, haematological tags were added to gene: ITGB3.
Mode of inheritance for gene: ITGB3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITGB3 were set to Glanzmann thrombasthenia 2, MIM# 619267
Review for gene: ITGB3 was set to GREEN
Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen.

GT can present soon after birth with episodic mucocutaneous bleeding, purpura, petechiae, unprovoked bruising, and excessive bleeding from the umbilical stump or post-circumcision. Major bleeding complications during the neonatal period, such as ICH following delivery are rare. The clinical severity of GT tends to diminish with age, although the bleeding manifestations persist and are life-long.

Recombinant activated factor VII (rFVIIa) may be considered for patients with: moderate to severe acute bleeding; for treatment of refractory minor bleeds; for prophylaxis in patients with frequent severe bleeds; treatment during minor and major surgery; and in patients who are refractory to platelet transfusion. Some guidelines suggest utilizing rFVIIa as a first line therapy and saving platelet transfusion for more severe or non-responsive bleeds. High doses have been successful, particularly if used early and upfront. rFVIIa in a dose of =80 µg/kg at intervals of 2.5 h or less were observed to be safe and effective in nonsurgical bleeds, minor and major procedures in patients with or without antibodies, and/or refractoriness.

The International Glanzmann Thrombasthenia Registry (GTR), published in 2015, studied 184 patients with 829 bleeding episodes and 96 patients with 206 surgical interventions. rFVIIa alone was used in 124/829 bleeds and the proportion of successful treatment to stop bleeding was 91%. In patients without antibodies/refractoriness, rFVIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for 24 minor and 4 major procedures. The lowest effectiveness of rFVIIa treatment alone was 88.9% (16/18 effective minor procedures) in refractory patients with platelet antibodies.

Desmopressin (DDAVP) may be considered as an additional treatment for mild bleeding episodes. DDAVP has been shown to be effective in many bleeding disorders, including inherited platelet function disorders. However, DDAVP efficacy among GT patients has not been established and guideline recommendations are conflicting.
Sources: ClinGen
BabyScreen+ newborn screening v0.1723 ITGA2B Zornitza Stark Marked gene: ITGA2B as ready
BabyScreen+ newborn screening v0.1723 ITGA2B Zornitza Stark Gene: itga2b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1723 ITGA2B Zornitza Stark Classified gene: ITGA2B as Green List (high evidence)
BabyScreen+ newborn screening v0.1723 ITGA2B Zornitza Stark Gene: itga2b has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1722 ITGA2B Zornitza Stark gene: ITGA2B was added
gene: ITGA2B was added to gNBS. Sources: ClinGen
treatable, haematological tags were added to gene: ITGA2B.
Mode of inheritance for gene: ITGA2B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITGA2B were set to Glanzmann thrombasthaenia 1, MIM# 273800
Review for gene: ITGA2B was set to GREEN
Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen.

GT can present soon after birth with episodic mucocutaneous bleeding, purpura, petechiae, unprovoked bruising, and excessive bleeding from the umbilical stump or post-circumcision. Major bleeding complications during the neonatal period, such as ICH following delivery are rare. The clinical severity of GT tends to diminish with age, although the bleeding manifestations persist and are life-long.

Recombinant activated factor VII (rFVIIa) may be considered for patients with: moderate to severe acute bleeding; for treatment of refractory minor bleeds; for prophylaxis in patients with frequent severe bleeds; treatment during minor and major surgery; and in patients who are refractory to platelet transfusion. Some guidelines suggest utilizing rFVIIa as a first line therapy and saving platelet transfusion for more severe or non-responsive bleeds. High doses have been successful, particularly if used early and upfront. rFVIIa in a dose of =80 µg/kg at intervals of 2.5 h or less were observed to be safe and effective in nonsurgical bleeds, minor and major procedures in patients with or without antibodies, and/or refractoriness.

The International Glanzmann Thrombasthenia Registry (GTR), published in 2015, studied 184 patients with 829 bleeding episodes and 96 patients with 206 surgical interventions. rFVIIa alone was used in 124/829 bleeds and the proportion of successful treatment to stop bleeding was 91%. In patients without antibodies/refractoriness, rFVIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for 24 minor and 4 major procedures. The lowest effectiveness of rFVIIa treatment alone was 88.9% (16/18 effective minor procedures) in refractory patients with platelet antibodies.

Desmopressin (DDAVP) may be considered as an additional treatment for mild bleeding episodes. DDAVP has been shown to be effective in many bleeding disorders, including inherited platelet function disorders. However, DDAVP efficacy among GT patients has not been established and guideline recommendations are conflicting.
Sources: ClinGen
BabyScreen+ newborn screening v0.1721 F7 Zornitza Stark Tag for review was removed from gene: F7.
BabyScreen+ newborn screening v0.1721 F7 Zornitza Stark changed review comment from: Well established gene-disease association.

Variable severity.

Treatment: Recombinant coagulation Factor VIIa

Non-genetic confirmatory testing: factor VII level; to: Well established gene-disease association.

Variable severity.

Treatment: Recombinant coagulation Factor VIIa

Non-genetic confirmatory testing: factor VII level

Rated as 'strong actionability' in paediatric patients by ClinGen.

Clinical expression of factor VII deficiency is highly variable, and no consistent relationship has been found between the severity of the hemorrhagic syndrome and the residual levels of FVII activity. Individuals can be completely asymptomatic despite a very low FVII level. A bleeding history appears more predictive of further bleeding than the factor VII level. Factor VII levels increase during pregnancy, but levels usually remain insufficient for hemostasis in severely affected cases. Individuals with no history of bleeding do not appear to be at increased risk of PPH. Heterozygotes often have approximately half-normal levels of coagulation factors and are often asymptomatic. However, up to 2% of patients with severe bleeding phenotype are heterozygotes.

Consider prophylaxis using rFVIIa in certain circumstances. Long term prophylaxis should be considered for cases with a personal or family history of severe bleeding or with FVII activity <0.01 IU/ml using rFVIIa, adjusting to maintain clinical response. Short term prophylaxis should be considered for cases for neonates without a personal or family history of severe bleeding but who have FVII activity 0.01-0.05 IU/ml up to 6-12 months of age.
BabyScreen+ newborn screening v0.1721 ABCC8 Zornitza Stark Marked gene: ABCC8 as ready
BabyScreen+ newborn screening v0.1721 ABCC8 Zornitza Stark Gene: abcc8 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1721 ABCC8 Zornitza Stark Tag treatable tag was added to gene: ABCC8.
Tag endocrine tag was added to gene: ABCC8.
BabyScreen+ newborn screening v0.1721 ABCC8 Zornitza Stark reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diabetes mellitus, permanent neonatal 3, with or without neurologic features, MIM 618857; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1721 COL9A2 Zornitza Stark Tag treatable tag was added to gene: COL9A2.
Tag ophthalmological tag was added to gene: COL9A2.
BabyScreen+ newborn screening v0.1721 COL9A2 Zornitza Stark edited their review of gene: COL9A2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1721 COL9A2 Zornitza Stark reviewed gene: COL9A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21671392, 31090205, 33356723; Phenotypes: Stickler syndrome, type V, MIM 614284; Mode of inheritance: None
BabyScreen+ newborn screening v0.1721 COL9A1 Zornitza Stark Marked gene: COL9A1 as ready
BabyScreen+ newborn screening v0.1721 COL9A1 Zornitza Stark Gene: col9a1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1721 COL9A1 Zornitza Stark Tag treatable tag was added to gene: COL9A1.
Tag ophthalmological tag was added to gene: COL9A1.
BabyScreen+ newborn screening v0.1721 TFAP2B Zornitza Stark Marked gene: TFAP2B as ready
BabyScreen+ newborn screening v0.1721 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1721 TFAP2B Zornitza Stark Phenotypes for gene: TFAP2B were changed from Char syndrome to Char syndrome, MIM 169100
BabyScreen+ newborn screening v0.1720 TFAP2B Zornitza Stark Classified gene: TFAP2B as Red List (low evidence)
BabyScreen+ newborn screening v0.1720 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1719 TFAP2B Zornitza Stark reviewed gene: TFAP2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Char syndrome, MIM 169100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1719 TFAP2A Zornitza Stark Marked gene: TFAP2A as ready
BabyScreen+ newborn screening v0.1719 TFAP2A Zornitza Stark Gene: tfap2a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1719 TFAP2A Zornitza Stark Phenotypes for gene: TFAP2A were changed from Branchiooculofacial syndrome to Branchiooculofacial syndrome, MIM 107580
BabyScreen+ newborn screening v0.1718 TFAP2A Zornitza Stark Classified gene: TFAP2A as Red List (low evidence)
BabyScreen+ newborn screening v0.1718 TFAP2A Zornitza Stark Gene: tfap2a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1717 TFAP2A Zornitza Stark reviewed gene: TFAP2A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Branchiooculofacial syndrome, MIM 107580; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1717 TECTA Zornitza Stark Marked gene: TECTA as ready
BabyScreen+ newborn screening v0.1717 TECTA Zornitza Stark Gene: tecta has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1717 TECTA Zornitza Stark Phenotypes for gene: TECTA were changed from Deafness to Deafness, autosomal recessive 21 603629; Deafness, autosomal dominant 8/12 601543
BabyScreen+ newborn screening v0.1716 TECTA Zornitza Stark Mode of inheritance for gene: TECTA was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1715 TECTA Zornitza Stark Tag deafness tag was added to gene: TECTA.
BabyScreen+ newborn screening v0.1715 TCN2 Zornitza Stark Publications for gene: TCN2 were set to
BabyScreen+ newborn screening v0.1714 TCN2 Zornitza Stark Tag treatable tag was added to gene: TCN2.
Tag metabolic tag was added to gene: TCN2.
BabyScreen+ newborn screening v0.1714 TCIRG1 Zornitza Stark Tag treatable tag was added to gene: TCIRG1.
Tag skeletal tag was added to gene: TCIRG1.
BabyScreen+ newborn screening v0.1714 TCF3 Zornitza Stark Tag treatable tag was added to gene: TCF3.
Tag immunological tag was added to gene: TCF3.
BabyScreen+ newborn screening v0.1714 TAT Zornitza Stark Tag metabolic tag was added to gene: TAT.
BabyScreen+ newborn screening v0.1714 STXBP2 Zornitza Stark Tag treatable tag was added to gene: STXBP2.
Tag immunological tag was added to gene: STXBP2.
BabyScreen+ newborn screening v0.1714 STX11 Zornitza Stark Tag treatable tag was added to gene: STX11.
Tag immunological tag was added to gene: STX11.
BabyScreen+ newborn screening v0.1714 STAT3 Zornitza Stark Tag treatable tag was added to gene: STAT3.
Tag immunological tag was added to gene: STAT3.
BabyScreen+ newborn screening v0.1714 STAR Zornitza Stark Tag treatable tag was added to gene: STAR.
Tag endocrine tag was added to gene: STAR.
BabyScreen+ newborn screening v0.1714 SRP54 Zornitza Stark Tag treatable tag was added to gene: SRP54.
Tag immunological tag was added to gene: SRP54.
BabyScreen+ newborn screening v0.1714 SPR Zornitza Stark Tag treatable tag was added to gene: SPR.
Tag neurological tag was added to gene: SPR.
BabyScreen+ newborn screening v0.1714 SP110 Zornitza Stark Tag treatable tag was added to gene: SP110.
Tag immunological tag was added to gene: SP110.
BabyScreen+ newborn screening v0.1714 SMPD1 Zornitza Stark Tag treatable tag was added to gene: SMPD1.
Tag metabolic tag was added to gene: SMPD1.
BabyScreen+ newborn screening v0.1714 SMN1 Zornitza Stark Tag neurological tag was added to gene: SMN1.
BabyScreen+ newborn screening v0.1714 SLC5A7 Zornitza Stark Tag treatable tag was added to gene: SLC5A7.
Tag neurological tag was added to gene: SLC5A7.
BabyScreen+ newborn screening v0.1714 SLC34A3 Zornitza Stark Tag skeletal tag was added to gene: SLC34A3.
BabyScreen+ newborn screening v0.1714 SLC26A3 Zornitza Stark Tag treatable tag was added to gene: SLC26A3.
Tag gastrointestinal tag was added to gene: SLC26A3.
BabyScreen+ newborn screening v0.1714 SLC25A15 Zornitza Stark Tag treatable tag was added to gene: SLC25A15.
Tag metabolic tag was added to gene: SLC25A15.
BabyScreen+ newborn screening v0.1712 SLC22A5 Zornitza Stark Tag metabolic tag was added to gene: SLC22A5.
BabyScreen+ newborn screening v0.1712 SLC19A3 Zornitza Stark Tag metabolic tag was added to gene: SLC19A3.
BabyScreen+ newborn screening v0.1712 SLC19A2 Zornitza Stark Tag metabolic tag was added to gene: SLC19A2.
BabyScreen+ newborn screening v0.1712 SLC18A3 Zornitza Stark Tag treatable tag was added to gene: SLC18A3.
Tag neurological tag was added to gene: SLC18A3.
BabyScreen+ newborn screening v0.1712 SLC12A1 Zornitza Stark Tag treatable tag was added to gene: SLC12A1.
Tag renal tag was added to gene: SLC12A1.
BabyScreen+ newborn screening v0.1712 SI Zornitza Stark Tag treatable tag was added to gene: SI.
Tag gastrointestinal tag was added to gene: SI.
BabyScreen+ newborn screening v0.1712 SH2D1A Zornitza Stark Tag treatable tag was added to gene: SH2D1A.
Tag immunological tag was added to gene: SH2D1A.
BabyScreen+ newborn screening v0.1712 SCNN1B Zornitza Stark Tag treatable tag was added to gene: SCNN1B.
Tag endocrine tag was added to gene: SCNN1B.
BabyScreen+ newborn screening v0.1712 SCNN1A Zornitza Stark Tag endocrine tag was added to gene: SCNN1A.
BabyScreen+ newborn screening v0.1712 SBDS Zornitza Stark Tag haematological tag was added to gene: SBDS.
Tag gastrointestinal tag was added to gene: SBDS.
BabyScreen+ newborn screening v0.1712 SAMHD1 Zornitza Stark Tag for review tag was added to gene: SAMHD1.
Tag neurological tag was added to gene: SAMHD1.
BabyScreen+ newborn screening v0.1712 RET Zornitza Stark Marked gene: RET as ready
BabyScreen+ newborn screening v0.1712 RET Zornitza Stark Gene: ret has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1712 RDX Zornitza Stark Tag deafness tag was added to gene: RDX.
BabyScreen+ newborn screening v0.1712 QDPR Zornitza Stark Tag metabolic tag was added to gene: QDPR.
BabyScreen+ newborn screening v0.1712 PTS Zornitza Stark Tag metabolic tag was added to gene: PTS.
BabyScreen+ newborn screening v0.1712 PSPH Zornitza Stark Marked gene: PSPH as ready
BabyScreen+ newborn screening v0.1712 PSPH Zornitza Stark Gene: psph has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1712 PSPH Zornitza Stark Publications for gene: PSPH were set to
BabyScreen+ newborn screening v0.1711 PSPH Zornitza Stark Classified gene: PSPH as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1711 PSPH Zornitza Stark Gene: psph has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1710 PSPH Zornitza Stark edited their review of gene: PSPH: Changed publications: 16763900, 26589312
BabyScreen+ newborn screening v0.1710 PSPH Zornitza Stark Tag for review tag was added to gene: PSPH.
BabyScreen+ newborn screening v0.1710 PSPH Zornitza Stark reviewed gene: PSPH: Rating: AMBER; Mode of pathogenicity: None; Publications: 26589312; Phenotypes: Phosphoserine phosphatase deficiency MIM#614023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1710 PKLR Zornitza Stark Tag treatable tag was added to gene: PKLR.
Tag metabolic tag was added to gene: PKLR.
BabyScreen+ newborn screening v0.1710 PHKG2 Zornitza Stark Tag metabolic tag was added to gene: PHKG2.
BabyScreen+ newborn screening v0.1710 PHKB Zornitza Stark Tag treatable tag was added to gene: PHKB.
Tag metabolic tag was added to gene: PHKB.
BabyScreen+ newborn screening v0.1710 PHKA2 Zornitza Stark Tag treatable tag was added to gene: PHKA2.
Tag metabolic tag was added to gene: PHKA2.
BabyScreen+ newborn screening v0.1710 PHGDH Zornitza Stark Tag metabolic tag was added to gene: PHGDH.
BabyScreen+ newborn screening v0.1710 PGM1 Zornitza Stark Tag metabolic tag was added to gene: PGM1.
BabyScreen+ newborn screening v0.1710 PDZD7 Zornitza Stark Tag deafness tag was added to gene: PDZD7.
BabyScreen+ newborn screening v0.1710 PDX1 Zornitza Stark Tag treatable tag was added to gene: PDX1.
Tag endocrine tag was added to gene: PDX1.
BabyScreen+ newborn screening v0.1710 PDHX Zornitza Stark Tag treatable tag was added to gene: PDHX.
Tag metabolic tag was added to gene: PDHX.
BabyScreen+ newborn screening v0.1710 PDHA1 Zornitza Stark Tag treatable tag was added to gene: PDHA1.
Tag metabolic tag was added to gene: PDHA1.
BabyScreen+ newborn screening v0.1710 PCDH15 Zornitza Stark Tag deafness tag was added to gene: PCDH15.
BabyScreen+ newborn screening v0.1710 PCCB Zornitza Stark Tag metabolic tag was added to gene: PCCB.
BabyScreen+ newborn screening v0.1710 PCCA Zornitza Stark Tag metabolic tag was added to gene: PCCA.
BabyScreen+ newborn screening v0.1710 PCBD1 Zornitza Stark Tag treatable tag was added to gene: PCBD1.
Tag metabolic tag was added to gene: PCBD1.
BabyScreen+ newborn screening v0.1710 PC Zornitza Stark Tag treatable tag was added to gene: PC.
Tag metabolic tag was added to gene: PC.
BabyScreen+ newborn screening v0.1710 PAX8 Zornitza Stark Tag treatable tag was added to gene: PAX8.
Tag endocrine tag was added to gene: PAX8.
BabyScreen+ newborn screening v0.1710 PAX3 Zornitza Stark Tag deafness tag was added to gene: PAX3.
BabyScreen+ newborn screening v0.1710 PALB2 Zornitza Stark Tag treatable tag was added to gene: PALB2.
Tag haematological tag was added to gene: PALB2.
BabyScreen+ newborn screening v0.1710 PAH Zornitza Stark Tag metabolic tag was added to gene: PAH.
BabyScreen+ newborn screening v0.1710 OXCT1 Zornitza Stark Tag metabolic tag was added to gene: OXCT1.
BabyScreen+ newborn screening v0.1710 OTOGL Zornitza Stark Tag deafness tag was added to gene: OTOGL.
BabyScreen+ newborn screening v0.1710 OTOF Zornitza Stark Tag deafness tag was added to gene: OTOF.
BabyScreen+ newborn screening v0.1710 OTOA Zornitza Stark Tag deafness tag was added to gene: OTOA.
BabyScreen+ newborn screening v0.1710 OTC Zornitza Stark Tag metabolic tag was added to gene: OTC.
BabyScreen+ newborn screening v0.1710 NR5A1 Zornitza Stark Tag endocrine tag was added to gene: NR5A1.
BabyScreen+ newborn screening v0.1710 NR3C2 Zornitza Stark Tag treatable tag was added to gene: NR3C2.
Tag endocrine tag was added to gene: NR3C2.
BabyScreen+ newborn screening v0.1710 NR0B1 Zornitza Stark Tag endocrine tag was added to gene: NR0B1.
BabyScreen+ newborn screening v0.1710 NPC2 Zornitza Stark Tag treatable tag was added to gene: NPC2.
Tag metabolic tag was added to gene: NPC2.
BabyScreen+ newborn screening v0.1710 NPC1 Zornitza Stark Tag treatable tag was added to gene: NPC1.
Tag metabolic tag was added to gene: NPC1.
BabyScreen+ newborn screening v0.1710 NNT Zornitza Stark Tag endocrine tag was added to gene: NNT.
BabyScreen+ newborn screening v0.1710 NKX2-1 Zornitza Stark Tag treatable tag was added to gene: NKX2-1.
Tag endocrine tag was added to gene: NKX2-1.
BabyScreen+ newborn screening v0.1710 NIPAL4 Zornitza Stark Tag for review tag was added to gene: NIPAL4.
BabyScreen+ newborn screening v0.1710 NIPAL4 Zornitza Stark commented on gene: NIPAL4: For review: treatment available?
BabyScreen+ newborn screening v0.1710 NHEJ1 Zornitza Stark Tag immunological tag was added to gene: NHEJ1.
BabyScreen+ newborn screening v0.1710 NF1 Zornitza Stark Tag for review tag was added to gene: NF1.
BabyScreen+ newborn screening v0.1710 NEUROG3 Zornitza Stark Tag gastrointestinal tag was added to gene: NEUROG3.
BabyScreen+ newborn screening v0.1710 NCF2 Zornitza Stark Tag immunological tag was added to gene: NCF2.
BabyScreen+ newborn screening v0.1710 NCF1 Zornitza Stark Tag immunological tag was added to gene: NCF1.
BabyScreen+ newborn screening v0.1710 NAGS Zornitza Stark Tag metabolic tag was added to gene: NAGS.
BabyScreen+ newborn screening v0.1710 NAGLU Zornitza Stark Tag metabolic tag was added to gene: NAGLU.
BabyScreen+ newborn screening v0.1710 MYSM1 Zornitza Stark Tag haematological tag was added to gene: MYSM1.
BabyScreen+ newborn screening v0.1710 MYO7A Zornitza Stark Tag deafness tag was added to gene: MYO7A.
BabyScreen+ newborn screening v0.1710 MYO6 Zornitza Stark Tag deafness tag was added to gene: MYO6.
BabyScreen+ newborn screening v0.1710 MYO15A Zornitza Stark Tag deafness tag was added to gene: MYO15A.
BabyScreen+ newborn screening v0.1710 MVK Zornitza Stark Tag metabolic tag was added to gene: MVK.
BabyScreen+ newborn screening v0.1710 MUT Zornitza Stark Tag metabolic tag was added to gene: MUT.
BabyScreen+ newborn screening v0.1710 MUSK Zornitza Stark Tag neurological tag was added to gene: MUSK.
BabyScreen+ newborn screening v0.1710 MTTP Zornitza Stark Tag metabolic tag was added to gene: MTTP.
BabyScreen+ newborn screening v0.1710 MTRR Zornitza Stark Tag treatable tag was added to gene: MTRR.
Tag metabolic tag was added to gene: MTRR.
BabyScreen+ newborn screening v0.1710 MTR Zornitza Stark Tag treatable tag was added to gene: MTR.
Tag haematological tag was added to gene: MTR.
BabyScreen+ newborn screening v0.1710 MRAP Zornitza Stark Tag endocrine tag was added to gene: MRAP.
BabyScreen+ newborn screening v0.1710 MPL Zornitza Stark Tag haematological tag was added to gene: MPL.
BabyScreen+ newborn screening v0.1710 MPI Zornitza Stark Tag metabolic tag was added to gene: MPI.
BabyScreen+ newborn screening v0.1710 MOCS1 Zornitza Stark Tag metabolic tag was added to gene: MOCS1.
BabyScreen+ newborn screening v0.1710 MMADHC Zornitza Stark Marked gene: MMADHC as ready
BabyScreen+ newborn screening v0.1710 MMADHC Zornitza Stark Gene: mmadhc has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1710 MMADHC Zornitza Stark Tag metabolic tag was added to gene: MMADHC.
BabyScreen+ newborn screening v0.1710 MMACHC Zornitza Stark Tag metabolic tag was added to gene: MMACHC.
BabyScreen+ newborn screening v0.1710 MMAB Zornitza Stark Tag metabolic tag was added to gene: MMAB.
BabyScreen+ newborn screening v0.1710 MMAA Zornitza Stark Tag metabolic tag was added to gene: MMAA.
BabyScreen+ newborn screening v0.1710 MLYCD Zornitza Stark Tag metabolic tag was added to gene: MLYCD.
BabyScreen+ newborn screening v0.1710 MITF Zornitza Stark Tag deafness tag was added to gene: MITF.
BabyScreen+ newborn screening v0.1710 MEFV Zornitza Stark Tag haematological tag was added to gene: MEFV.
BabyScreen+ newborn screening v0.1710 MCFD2 Zornitza Stark Tag haematological tag was added to gene: MCFD2.
BabyScreen+ newborn screening v0.1710 MC2R Zornitza Stark Tag endocrine tag was added to gene: MC2R.
BabyScreen+ newborn screening v0.1710 MARVELD2 Zornitza Stark Tag deafness tag was added to gene: MARVELD2.
BabyScreen+ newborn screening v0.1710 MAN2B1 Zornitza Stark Tag metabolic tag was added to gene: MAN2B1.
BabyScreen+ newborn screening v0.1710 TFAP2B David Amor reviewed gene: TFAP2B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: MIM 169100 Char syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1710 TFAP2A David Amor reviewed gene: TFAP2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: MIM 107580 Branchiooculofacial syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1710 COL9A1 David Amor changed review comment from: Gene-disease association: strong but rare, prbably <1% of Sticller syndrome; Van Camp et al. (2006) described a consanguineous Moroccan family in which 4 of 10 sibs had features characteristic of Stickler syndrome, including moderate to severe sensorineural hearing loss, moderate to high myopia with vitreoretinopathy, and epiphyseal dysplasia. Nikopoulos et al. (2011) reported 2 sisters in a Turkish family and 1 boy in a Moroccan family with features of autosomal recessive Stickler syndrome. All 3 individuals had myopia, vitreous changes, sensorineural hearing loss, and epiphyseal dysplasia. They also had exudative rhegmatogenous retinal detachment.

Severity: moderate-severe

Age of onset: congenital

Non-molecular confirmatory testing: Affected individuals have moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, cataracts, and epiphyseal dysplasia

Treatment: as per other Stickler syndrome; to: Gene-disease association: strong but rare, prbably <1% of Sticller syndrome; Van Camp et al. (2006) described a consanguineous Moroccan family in which 4 of 10 sibs had features characteristic of Stickler syndrome, including moderate to severe sensorineural hearing loss, moderate to high myopia with vitreoretinopathy, and epiphyseal dysplasia. Nikopoulos et al. (2011) reported 2 sisters in a Turkish family and 1 boy in a Moroccan family with features of autosomal recessive Stickler syndrome. All 3 individuals had myopia, vitreous changes, sensorineural hearing loss, and epiphyseal dysplasia. They also had exudative rhegmatogenous retinal detachment.

Severity: moderate-severe

Age of onset: congenital

Non-molecular confirmatory testing: Affected individuals have moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, cataracts, and epiphyseal dysplasia

Treatment: as per other Stickler syndrome
BabyScreen+ newborn screening v0.1710 COL9A2 David Amor reviewed gene: COL9A2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: MIM 614284 ?Stickler syndrome, type V; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1710 COL9A1 David Amor reviewed gene: COL9A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: MIM 120210 Stickler syndrome, type IV; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: MIM 256450 Hyperinsulinemic hypoglycemia, familial, 1, MIM 618857 Diabetes mellitus, permanent neonatal 3, with or without neurologic features; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor Deleted their review
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor Deleted their comment
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor Deleted their comment
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor commented on gene: ABCC8: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.

Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor edited their review of gene: ABCC8: Changed phenotypes: MIM 256450 Hyperinsulinemic hypoglycemia, familial, 1, MIM 618857 Diabetes mellitus, permanent neonatal 3, with or without neurologic features
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor Deleted their comment
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor commented on gene: ABCC8: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.

Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor changed review comment from: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.



Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
; to: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.

Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor changed review comment from: Gene-disease association: strong. Note sporadic cases with focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele

Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes, glucose, insulin, free fatty acid levels

Treatment: as per rx-genes, Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus; to: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.



Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
BabyScreen+ newborn screening v0.1710 ABCC8 David Amor reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: MIM 256450 Hyperinsulinemic hypoglycemia, familial, 1; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1710 TECTA David Amor reviewed gene: TECTA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 21, Deafness, autosomal dominant 8/12; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1710 LYST Zornitza Stark Tag immunological tag was added to gene: LYST.
BabyScreen+ newborn screening v0.1710 LRTOMT Zornitza Stark Tag deafness tag was added to gene: LRTOMT.
BabyScreen+ newborn screening v0.1710 LRP5 Zornitza Stark Tag treatable tag was added to gene: LRP5.
Tag skeletal tag was added to gene: LRP5.
BabyScreen+ newborn screening v0.1710 LOXHD1 Zornitza Stark Tag deafness tag was added to gene: LOXHD1.
BabyScreen+ newborn screening v0.1710 LMBRD1 Zornitza Stark Tag metabolic tag was added to gene: LMBRD1.
BabyScreen+ newborn screening v0.1710 LIPA Zornitza Stark Tag metabolic tag was added to gene: LIPA.
BabyScreen+ newborn screening v0.1710 LIG4 Zornitza Stark Tag treatable tag was added to gene: LIG4.
Tag immunological tag was added to gene: LIG4.
BabyScreen+ newborn screening v0.1710 LHX4 Zornitza Stark Tag endocrine tag was added to gene: LHX4.
BabyScreen+ newborn screening v0.1710 LHX3 Zornitza Stark Tag endocrine tag was added to gene: LHX3.
BabyScreen+ newborn screening v0.1710 LHFPL5 Zornitza Stark Tag deafness tag was added to gene: LHFPL5.
BabyScreen+ newborn screening v0.1710 LEPR Zornitza Stark Tag endocrine tag was added to gene: LEPR.
BabyScreen+ newborn screening v0.1710 LDLR Zornitza Stark Tag for review was removed from gene: LDLR.
Tag treatable tag was added to gene: LDLR.
Tag metabolic tag was added to gene: LDLR.
BabyScreen+ newborn screening v0.1710 L1CAM Zornitza Stark Marked gene: L1CAM as ready
BabyScreen+ newborn screening v0.1710 L1CAM Zornitza Stark Gene: l1cam has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1710 L1CAM Zornitza Stark Phenotypes for gene: L1CAM were changed from X-linked hydrocephalus syndrome to Hydrocephalus due to aqueductal stenosis, MIM# 307000
BabyScreen+ newborn screening v0.1709 L1CAM Zornitza Stark Classified gene: L1CAM as Red List (low evidence)
BabyScreen+ newborn screening v0.1709 L1CAM Zornitza Stark Gene: l1cam has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1708 KCNJ11 Zornitza Stark changed review comment from: Association with hyperinsulinism is well established.

Onset is congenital.

Treatment: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

Association with neonatal diabetes is also well established.

Treatment: Insulin, glibenclamide, oral pancreatic enzymes.

Phenotypes are expected to be distinguishable clinically.; to: Association with hyperinsulinism is well established, mono-allelic variants.

Onset is congenital.

Treatment: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

Association with neonatal diabetes is also well established, bi-allelic variants.

Treatment: Insulin, glibenclamide, oral pancreatic enzymes.

Phenotypes are expected to be distinguishable clinically.
BabyScreen+ newborn screening v0.1708 KCNJ11 Zornitza Stark Marked gene: KCNJ11 as ready
BabyScreen+ newborn screening v0.1708 KCNJ11 Zornitza Stark Gene: kcnj11 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1708 KCNJ11 Zornitza Stark Phenotypes for gene: KCNJ11 were changed from Hyperinsulinemic hypoglycemia, familial, MIM#601820 to Diabetes mellitus, transient neonatal, 3 610582; Diabetes, permanent neonatal, with or without neurologic features 606176; Hyperinsulinemic hypoglycemia, familial, 2 601820
BabyScreen+ newborn screening v0.1707 KCNJ11 Zornitza Stark Mode of inheritance for gene: KCNJ11 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1706 KCNJ11 Zornitza Stark Tag treatable tag was added to gene: KCNJ11.
Tag endocrine tag was added to gene: KCNJ11.
BabyScreen+ newborn screening v0.1706 KCNJ11 Zornitza Stark reviewed gene: KCNJ11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diabetes mellitus, transient neonatal, 3 610582, Diabetes, permanent neonatal, with or without neurologic features 606176, Hyperinsulinemic hypoglycemia, familial, 2 601820; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1706 KCNJ1 Zornitza Stark Tag treatable tag was added to gene: KCNJ1.
Tag renal tag was added to gene: KCNJ1.
BabyScreen+ newborn screening v0.1706 IVD Zornitza Stark Tag metabolic tag was added to gene: IVD.
BabyScreen+ newborn screening v0.1706 ILDR1 Zornitza Stark Tag deafness tag was added to gene: ILDR1.
BabyScreen+ newborn screening v0.1706 HMGCL Zornitza Stark Tag metabolic tag was added to gene: HMGCL.
BabyScreen+ newborn screening v0.1706 HLCS Zornitza Stark Tag metabolic tag was added to gene: HLCS.
BabyScreen+ newborn screening v0.1706 HK1 Zornitza Stark Tag treatable tag was added to gene: HK1.
Tag endocrine tag was added to gene: HK1.
BabyScreen+ newborn screening v0.1706 HGF Zornitza Stark Tag deafness tag was added to gene: HGF.
BabyScreen+ newborn screening v0.1706 HADHB Zornitza Stark Tag metabolic tag was added to gene: HADHB.
BabyScreen+ newborn screening v0.1706 HADHA Zornitza Stark Tag metabolic tag was added to gene: HADHA.
BabyScreen+ newborn screening v0.1706 GRXCR1 Zornitza Stark Tag deafness tag was added to gene: GRXCR1.
BabyScreen+ newborn screening v0.1706 GNS Zornitza Stark Marked gene: GNS as ready
BabyScreen+ newborn screening v0.1706 GNS Zornitza Stark Gene: gns has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1706 GNS Zornitza Stark Phenotypes for gene: GNS were changed from Mucopolysaccharidosis IIId to Mucopolysaccharidosis type IIID, MIM# 252940
BabyScreen+ newborn screening v0.1705 GNS Zornitza Stark Publications for gene: GNS were set to
BabyScreen+ newborn screening v0.1704 GNS Zornitza Stark Classified gene: GNS as Red List (low evidence)
BabyScreen+ newborn screening v0.1704 GNS Zornitza Stark Gene: gns has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1703 GNAS Zornitza Stark Mode of inheritance for gene: GNAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
BabyScreen+ newborn screening v0.1702 GNAS Zornitza Stark Marked gene: GNAS as ready
BabyScreen+ newborn screening v0.1702 GNAS Zornitza Stark Gene: gnas has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1702 GNAS Zornitza Stark Tag treatable tag was added to gene: GNAS.
Tag endocrine tag was added to gene: GNAS.
BabyScreen+ newborn screening v0.1702 GNAS Zornitza Stark reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudohypoparathyroidism Ia, MIM#103580 (Hypothyroidism); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
BabyScreen+ newborn screening v0.1702 GLRA1 Zornitza Stark Marked gene: GLRA1 as ready
BabyScreen+ newborn screening v0.1702 GLRA1 Zornitza Stark Gene: glra1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1702 GLRA1 Zornitza Stark Publications for gene: GLRA1 were set to
BabyScreen+ newborn screening v0.1701 GLRA1 Zornitza Stark Tag treatable tag was added to gene: GLRA1.
Tag neurological tag was added to gene: GLRA1.
BabyScreen+ newborn screening v0.1701 GLA Zornitza Stark Tag for review tag was added to gene: GLA.
BabyScreen+ newborn screening v0.1701 GLA Zornitza Stark edited their review of gene: GLA: Changed rating: AMBER; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1701 GLA Zornitza Stark changed review comment from: For review: screen only for males or include both?; to: Assessed as 'moderate actionability' in paediatric patients by ClinGen.

In classic FD, the first symptoms, including chronic neuropathic pain and episodic severe pain crises, emerge during childhood (typically age 3-10 years). Heterozygous females typically have a later median age of onset than males (9-13 years versus 13-23 years). Rarely, females may be relatively asymptomatic and have a normal life span or may have symptoms as severe as males with the classic phenotype.

Cardiac and/or cerebrovascular disease is present in most males by middle age while ESRD usually develops during the third to fifth decade. Renal and cardiac failure represent major sources of morbidity, and account for the reduced lifespan among affected males (50-58 years) and females (70-75 years) compared to the normal population.

A systematic review of RCTs of ERT reported on nine studies of 351 FD patients; however, many of these studies reported only on the effect of ERT on levels of enzyme substrate. Data from 2 trials (n=39 males) found no statistically significant differences in plasma enzyme substrate and one trial (n=24 males) found no statistical differences in renal function between individuals treated with agalsidase alfa and placebo (up to 6-month follow-up). Similar results were seen for agalsidase beta. One trial of 26 male patients found a statistically significant difference in pain, favoring agalsidase alfa compared to placebo at 5-6 months after treatment. No trial reported on the effect of agalsidase alfa on mortality or cardiac/cerebrovascular disease. One trial of agalsidase beta (n=82 males and females) found no difference in mortality, renal function, or symptoms or complications of cardiac or cerebrovascular disease over 18 months. The long-term influence of ERT on risk of morbidity and mortality related to FD remains to be established.

Migalastat, an oral chaperone drug, is recommended as an option for treatment for some patients with FD who are over 16 years with an amenable genetic variant who would usually be offered ERT. For non-amenable genotypes, migalastat may result in a net loss of alpha-Gal A activity, potentially worsening the disease condition.

A systematic review evaluated 2 phase III RCTs that both included males and females. One RCT randomized patients to switch from ERT to migalastat (n = 36) or continue with ERT (n = 24) during an 18-month period with a 12-month extension in which all patients received migalastat. During the treatment period, the percentage of patients who had a renal, cardiac, or cerebrovascular event or died was 29% of patients on migalastat compared to 44% of patients on ERT. However, this difference was not statistically significant. A second RCT compared migalastat (n=34) with placebo (n=33) over a 6-month period, with an 18-month extension study. The primary outcome was change from baseline in interstitial capillary inclusions of the enzyme substrate globotriaosylceramide (GL-3), which was not significantly different between groups. Results from both trials indicate that migalastat does not have a significant beneficial effect on pain, health-related quality of life outcomes, or glomerular filtration rate (results were uncertain due to large confidence intervals, small sample sizes, and/or short follow-up time). Migalastat did not influence left ventricular ejection fraction but did improve left ventricular mass over 18 months.

There are a number of recommendations for surveillance and agents to avoid (amiodarone). There is no consensus as to when ERT should be started.
BabyScreen+ newborn screening v0.1701 GJB2 Zornitza Stark Marked gene: GJB2 as ready
BabyScreen+ newborn screening v0.1701 GJB2 Zornitza Stark Gene: gjb2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1701 GJB2 Zornitza Stark Phenotypes for gene: GJB2 were changed from Deafness and palmoplantar keratoderma; Deafness to Deafness, autosomal recessive 1A, MIM# 220290
BabyScreen+ newborn screening v0.1700 GJB2 Zornitza Stark Mode of inheritance for gene: GJB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1699 GJB2 Zornitza Stark Tag deafness tag was added to gene: GJB2.
BabyScreen+ newborn screening v0.1699 GJB2 Zornitza Stark reviewed gene: GJB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 1A, MIM# 220290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1699 GIPC3 Zornitza Stark Tag deafness tag was added to gene: GIPC3.
BabyScreen+ newborn screening v0.1699 GCM2 Zornitza Stark Tag treatable tag was added to gene: GCM2.
Tag endocrine tag was added to gene: GCM2.
BabyScreen+ newborn screening v0.1699 GCK Zornitza Stark Tag treatable tag was added to gene: GCK.
Tag endocrine tag was added to gene: GCK.
BabyScreen+ newborn screening v0.1699 GCDH Zornitza Stark Tag metabolic tag was added to gene: GCDH.
BabyScreen+ newborn screening v0.1699 GBA Zornitza Stark Tag metabolic tag was added to gene: GBA.
BabyScreen+ newborn screening v0.1699 GATA4 Zornitza Stark Phenotypes for gene: GATA4 were changed from Atrial septal defect 2 MIM#607941; Atrioventricular septal defect 4 MIM#614430; Ventricular septal defect 1 MIM#614429 to Neonatal diabetes mellitus, MONDO:0016391, GATA4-related
BabyScreen+ newborn screening v0.1698 GATA4 Zornitza Stark Tag treatable tag was added to gene: GATA4.
Tag endocrine tag was added to gene: GATA4.
BabyScreen+ newborn screening v0.1698 GATA4 Zornitza Stark changed review comment from: Expect to be able to distinguish between the two phenotypes clinically in the newborn period.; to: Expect to be able to distinguish between the two phenotypes clinically in the newborn period.

Included here for association with neonatal diabetes.
BabyScreen+ newborn screening v0.1698 GATA3 Zornitza Stark Tag endocrine tag was added to gene: GATA3.
Tag deafness tag was added to gene: GATA3.
BabyScreen+ newborn screening v0.1698 GATA2 Zornitza Stark Tag haematological tag was added to gene: GATA2.
Tag deafness tag was added to gene: GATA2.
BabyScreen+ newborn screening v0.1698 GAMT Zornitza Stark Tag metabolic tag was added to gene: GAMT.
BabyScreen+ newborn screening v0.1698 GALT Zornitza Stark Tag metabolic tag was added to gene: GALT.
BabyScreen+ newborn screening v0.1698 GALNS Zornitza Stark Tag metabolic tag was added to gene: GALNS.
BabyScreen+ newborn screening v0.1698 GALK1 Zornitza Stark Tag metabolic tag was added to gene: GALK1.
BabyScreen+ newborn screening v0.1698 GALE Zornitza Stark Tag metabolic tag was added to gene: GALE.
BabyScreen+ newborn screening v0.1698 GALC Zornitza Stark Tag metabolic tag was added to gene: GALC.
BabyScreen+ newborn screening v0.1698 GAA Zornitza Stark Tag metabolic tag was added to gene: GAA.
BabyScreen+ newborn screening v0.1698 G6PD Zornitza Stark Tag treatable tag was added to gene: G6PD.
Tag haematological tag was added to gene: G6PD.
BabyScreen+ newborn screening v0.1698 G6PC3 Zornitza Stark Tag immunological tag was added to gene: G6PC3.
BabyScreen+ newborn screening v0.1698 G6PC Zornitza Stark Tag metabolic tag was added to gene: G6PC.
BabyScreen+ newborn screening v0.1698 FUCA1 Zornitza Stark Tag metabolic tag was added to gene: FUCA1.
BabyScreen+ newborn screening v0.1698 FOXP3 Zornitza Stark Tag immunological tag was added to gene: FOXP3.
BabyScreen+ newborn screening v0.1698 FOXA2 Zornitza Stark Tag treatable tag was added to gene: FOXA2.
Tag endocrine tag was added to gene: FOXA2.
BabyScreen+ newborn screening v0.1698 FLAD1 Zornitza Stark Tag metabolic tag was added to gene: FLAD1.
BabyScreen+ newborn screening v0.1698 FH Zornitza Stark Tag metabolic tag was added to gene: FH.
BabyScreen+ newborn screening v0.1698 FGG Zornitza Stark Tag haematological tag was added to gene: FGG.
BabyScreen+ newborn screening v0.1698 FGFR3 Zornitza Stark Tag skeletal tag was added to gene: FGFR3.
BabyScreen+ newborn screening v0.1698 FGF3 Zornitza Stark Tag deafness tag was added to gene: FGF3.
BabyScreen+ newborn screening v0.1698 FGB Zornitza Stark Tag treatable tag was added to gene: FGB.
Tag haematological tag was added to gene: FGB.
BabyScreen+ newborn screening v0.1698 FGA Zornitza Stark Tag treatable tag was added to gene: FGA.
Tag haematological tag was added to gene: FGA.
BabyScreen+ newborn screening v0.1698 FERMT3 Zornitza Stark Tag immunological tag was added to gene: FERMT3.
BabyScreen+ newborn screening v0.1698 FBP1 Zornitza Stark Tag treatable tag was added to gene: FBP1.
Tag metabolic tag was added to gene: FBP1.
BabyScreen+ newborn screening v0.1698 FANCI Zornitza Stark Tag haematological tag was added to gene: FANCI.
BabyScreen+ newborn screening v0.1698 FANCG Zornitza Stark Tag haematological tag was added to gene: FANCG.
BabyScreen+ newborn screening v0.1698 FANCD2 Zornitza Stark Tag treatable tag was added to gene: FANCD2.
Tag haematological tag was added to gene: FANCD2.
BabyScreen+ newborn screening v0.1698 FANCC Zornitza Stark Tag treatable tag was added to gene: FANCC.
Tag haematological tag was added to gene: FANCC.
BabyScreen+ newborn screening v0.1698 FANCB Zornitza Stark Tag haematological tag was added to gene: FANCB.
BabyScreen+ newborn screening v0.1698 FANCA Zornitza Stark Tag treatable tag was added to gene: FANCA.
Tag haematological tag was added to gene: FANCA.
BabyScreen+ newborn screening v0.1698 FAH Zornitza Stark Tag metabolic tag was added to gene: FAH.
BabyScreen+ newborn screening v0.1698 F9 Zornitza Stark Marked gene: F9 as ready
BabyScreen+ newborn screening v0.1698 F9 Zornitza Stark Gene: f9 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1698 F9 Zornitza Stark Tag treatable tag was added to gene: F9.
Tag haematological tag was added to gene: F9.
BabyScreen+ newborn screening v0.1698 F9 Zornitza Stark reviewed gene: F9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Haemophilia B (MIM#306900); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1698 F8 Zornitza Stark Marked gene: F8 as ready
BabyScreen+ newborn screening v0.1698 F8 Zornitza Stark Gene: f8 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1698 F8 Zornitza Stark Tag for review tag was added to gene: F8.
Tag treatable tag was added to gene: F8.
Tag haematological tag was added to gene: F8.
BabyScreen+ newborn screening v0.1698 F8 Zornitza Stark reviewed gene: F8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Haemophilia A, MIM# 306700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1698 F7 Zornitza Stark Marked gene: F7 as ready
BabyScreen+ newborn screening v0.1698 F7 Zornitza Stark Gene: f7 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1698 F7 Zornitza Stark Tag for review tag was added to gene: F7.
Tag treatable tag was added to gene: F7.
Tag haematological tag was added to gene: F7.
BabyScreen+ newborn screening v0.1698 F7 Zornitza Stark edited their review of gene: F7: Changed rating: GREEN
BabyScreen+ newborn screening v0.1698 F7 Zornitza Stark reviewed gene: F7: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor VII deficiency, MIM# 227500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1698 FGF23 Zornitza Stark Marked gene: FGF23 as ready
BabyScreen+ newborn screening v0.1698 FGF23 Zornitza Stark Gene: fgf23 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1698 FGF23 Zornitza Stark Classified gene: FGF23 as Green List (high evidence)
BabyScreen+ newborn screening v0.1698 FGF23 Zornitza Stark Gene: fgf23 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1697 FGF23 Zornitza Stark Tag treatable tag was added to gene: FGF23.
Tag endocrine tag was added to gene: FGF23.
BabyScreen+ newborn screening v0.1697 FGF23 Zornitza Stark gene: FGF23 was added
gene: FGF23 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: FGF23 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: FGF23 were set to autosomal dominant hypophosphatemic rickets MONDO:0008660; familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome MONDO:0100251
Review for gene: FGF23 was set to GREEN
Added comment: Mono-allelic GoF variants are associated with hypophosphataemic rickets.

Onset in some is in infancy (others adolescence).

Treatment: phosphate supplementation and calcitriol

Non-genetic confirmatory testing: serum phosphate, calcium, PTH, alkaline phosphatase levels, urine calcium level

Bi-allelic LoF variants are associated with tumoral calcinosis.

Age of onset and severity are variable, but include early childhood.

Treatment: dietary restriction, antacids, phosphate binders, acetazolamide, hemodialysis

Non-genetic confirmatory testing: serum phosphate, calcium, PTH, alkaline phosphatase, vitamin D serum levels, urine calcium, phosphate levels, plasma levels of the C-terminal portion of the phosphate-regulating hormone, fibroblast growth factor 23
Sources: Expert list
BabyScreen+ newborn screening v0.1696 F5 Zornitza Stark Marked gene: F5 as ready
BabyScreen+ newborn screening v0.1696 F5 Zornitza Stark Gene: f5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1696 F5 Zornitza Stark Phenotypes for gene: F5 were changed from Factor V deficiency MIM# 227400; Thrombophilia due to activated protein C resistance MIM# 188055 to Factor V deficiency, MIM# 227400 MONDO:0009210; Thrombophilia due to activated protein C resistance, MIM# 188055 MONDO:0008560; {Thrombophilia, susceptibility to, due to factor V Leiden}, MIM# 188055
BabyScreen+ newborn screening v0.1695 F5 Zornitza Stark Classified gene: F5 as Red List (low evidence)
BabyScreen+ newborn screening v0.1695 F5 Zornitza Stark Gene: f5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1694 F5 Zornitza Stark reviewed gene: F5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor V deficiency, MIM# 227400 MONDO:0009210, Thrombophilia due to activated protein C resistance, MIM# 188055 MONDO:0008560, {Thrombophilia, susceptibility to, due to factor V Leiden}, MIM# 188055; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1694 F2 Zornitza Stark Marked gene: F2 as ready
BabyScreen+ newborn screening v0.1694 F2 Zornitza Stark Gene: f2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1694 F2 Zornitza Stark Phenotypes for gene: F2 were changed from Prothrombin deficiency, MIM#613679 to Dysprothrombinemia MIM#613679; Hypoprothrombinemia MIM#613679; Thrombophilia due to thrombin defect MIM#188050
BabyScreen+ newborn screening v0.1693 F2 Zornitza Stark Mode of inheritance for gene: F2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1692 F2 Zornitza Stark Classified gene: F2 as Red List (low evidence)
BabyScreen+ newborn screening v0.1692 F2 Zornitza Stark Gene: f2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1691 F2 Zornitza Stark reviewed gene: F2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dysprothrombinemia MIM#613679, Hypoprothrombinemia MIM#613679, Thrombophilia due to thrombin defect MIM#188050; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1691 F13A1 Zornitza Stark Marked gene: F13A1 as ready
BabyScreen+ newborn screening v0.1691 F13A1 Zornitza Stark Gene: f13a1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1691 F13A1 Zornitza Stark Tag treatable tag was added to gene: F13A1.
Tag haematological tag was added to gene: F13A1.
BabyScreen+ newborn screening v0.1691 F13A1 Zornitza Stark reviewed gene: F13A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor XIIIA deficiency, MIM# 613225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1691 F11 Zornitza Stark Marked gene: F11 as ready
BabyScreen+ newborn screening v0.1691 F11 Zornitza Stark Gene: f11 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1691 F11 Zornitza Stark Phenotypes for gene: F11 were changed from Factor XI deficiency to Factor XI deficiency, autosomal dominant 612416; Factor XI deficiency, autosomal recessive, MIM#612416
BabyScreen+ newborn screening v0.1690 F11 Zornitza Stark Mode of inheritance for gene: F11 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1689 F11 Zornitza Stark Classified gene: F11 as Red List (low evidence)
BabyScreen+ newborn screening v0.1689 F11 Zornitza Stark Gene: f11 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1688 F11 Zornitza Stark reviewed gene: F11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor XI deficiency, autosomal dominant 612416, Factor XI deficiency, autosomal recessive, MIM#612416; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1688 ETHE1 Zornitza Stark Tag metabolic tag was added to gene: ETHE1.
BabyScreen+ newborn screening v0.1688 ETFDH Zornitza Stark Tag metabolic tag was added to gene: ETFDH.
BabyScreen+ newborn screening v0.1688 ETFB Zornitza Stark Tag treatable tag was added to gene: ETFB.
Tag metabolic tag was added to gene: ETFB.
BabyScreen+ newborn screening v0.1688 ETFA Zornitza Stark Tag metabolic tag was added to gene: ETFA.
BabyScreen+ newborn screening v0.1688 ESRRB Zornitza Stark Tag deafness tag was added to gene: ESRRB.
BabyScreen+ newborn screening v0.1688 ESPN Zornitza Stark Tag deafness tag was added to gene: ESPN.
BabyScreen+ newborn screening v0.1688 EPS8 Zornitza Stark Tag deafness tag was added to gene: EPS8.
BabyScreen+ newborn screening v0.1688 ENPP1 Zornitza Stark Tag endocrine tag was added to gene: ENPP1.
Tag vascular tag was added to gene: ENPP1.
BabyScreen+ newborn screening v0.1688 ENG Zornitza Stark Tag treatable tag was added to gene: ENG.
Tag vascular tag was added to gene: ENG.
BabyScreen+ newborn screening v0.1688 ELANE Zornitza Stark Tag treatable tag was added to gene: ELANE.
Tag immunological tag was added to gene: ELANE.
BabyScreen+ newborn screening v0.1688 EIF2AK3 Zornitza Stark Tag treatable tag was added to gene: EIF2AK3.
Tag endocrine tag was added to gene: EIF2AK3.
BabyScreen+ newborn screening v0.1688 EFL1 Zornitza Stark Tag gastrointestinal tag was added to gene: EFL1.
BabyScreen+ newborn screening v0.1688 EDNRB Zornitza Stark Tag deafness tag was added to gene: EDNRB.
BabyScreen+ newborn screening v0.1688 EDN3 Zornitza Stark Tag deafness tag was added to gene: EDN3.
BabyScreen+ newborn screening v0.1688 DUOXA2 Zornitza Stark Tag endocrine tag was added to gene: DUOXA2.
BabyScreen+ newborn screening v0.1688 DUOX2 Zornitza Stark Tag endocrine tag was added to gene: DUOX2.
BabyScreen+ newborn screening v0.1688 DPAGT1 Zornitza Stark Tag treatable tag was added to gene: DPAGT1.
Tag neurological tag was added to gene: DPAGT1.
BabyScreen+ newborn screening v0.1688 DOK7 Zornitza Stark Tag neurological tag was added to gene: DOK7.
BabyScreen+ newborn screening v0.1688 DOCK8 Zornitza Stark Tag immunological tag was added to gene: DOCK8.
BabyScreen+ newborn screening v0.1688 DNMT3B Zornitza Stark Tag immunological tag was added to gene: DNMT3B.
BabyScreen+ newborn screening v0.1688 DNAJB6 Zornitza Stark Classified gene: DNAJB6 as Red List (low evidence)
BabyScreen+ newborn screening v0.1688 DNAJB6 Zornitza Stark Gene: dnajb6 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1687 DNAJB6 Zornitza Stark edited their review of gene: DNAJB6: Changed rating: RED
BabyScreen+ newborn screening v0.1687 DMP1 Zornitza Stark Tag treatable tag was added to gene: DMP1.
Tag skeletal tag was added to gene: DMP1.
BabyScreen+ newborn screening v0.1687 DHCR7 Zornitza Stark Tag metabolic tag was added to gene: DHCR7.
BabyScreen+ newborn screening v0.1687 DGAT1 Zornitza Stark Tag gastrointestinal tag was added to gene: DGAT1.
BabyScreen+ newborn screening v0.1687 DFNB59 Zornitza Stark Tag deafness tag was added to gene: DFNB59.
BabyScreen+ newborn screening v0.1687 DDC Zornitza Stark Tag metabolic tag was added to gene: DDC.
BabyScreen+ newborn screening v0.1687 DCLRE1C Zornitza Stark Tag immunological tag was added to gene: DCLRE1C.
BabyScreen+ newborn screening v0.1687 DBT Zornitza Stark Tag metabolic tag was added to gene: DBT.
BabyScreen+ newborn screening v0.1687 CYP27B1 Zornitza Stark Tag endocrine tag was added to gene: CYP27B1.
BabyScreen+ newborn screening v0.1687 CYP17A1 Zornitza Stark Tag endocrine tag was added to gene: CYP17A1.
BabyScreen+ newborn screening v0.1687 CYP11B2 Zornitza Stark Tag endocrine tag was added to gene: CYP11B2.
BabyScreen+ newborn screening v0.1687 CYP11B1 Zornitza Stark Tag endocrine tag was added to gene: CYP11B1.
BabyScreen+ newborn screening v0.1687 CYP11A1 Zornitza Stark Tag endocrine tag was added to gene: CYP11A1.
BabyScreen+ newborn screening v0.1687 CYBB Zornitza Stark Tag immunological tag was added to gene: CYBB.
BabyScreen+ newborn screening v0.1687 CYBA Zornitza Stark Tag immunological tag was added to gene: CYBA.
BabyScreen+ newborn screening v0.1687 CXCR4 Zornitza Stark Tag immunological tag was added to gene: CXCR4.
BabyScreen+ newborn screening v0.1687 CUBN Zornitza Stark Tag haematological tag was added to gene: CUBN.
BabyScreen+ newborn screening v0.1687 CTPS1 Zornitza Stark Tag immunological tag was added to gene: CTPS1.
BabyScreen+ newborn screening v0.1687 CTNS Zornitza Stark Tag renal tag was added to gene: CTNS.
BabyScreen+ newborn screening v0.1687 CSF3R Zornitza Stark Tag immunological tag was added to gene: CSF3R.
BabyScreen+ newborn screening v0.1687 CRTAP Zornitza Stark Tag treatable tag was added to gene: CRTAP.
Tag skeletal tag was added to gene: CRTAP.
BabyScreen+ newborn screening v0.1687 CPT2 Zornitza Stark Tag metabolic tag was added to gene: CPT2.
BabyScreen+ newborn screening v0.1687 CPT1A Zornitza Stark Tag metabolic tag was added to gene: CPT1A.
BabyScreen+ newborn screening v0.1687 CPS1 Zornitza Stark Tag metabolic tag was added to gene: CPS1.
BabyScreen+ newborn screening v0.1687 COQ8A Zornitza Stark Tag metabolic tag was added to gene: COQ8A.
BabyScreen+ newborn screening v0.1687 COQ4 Zornitza Stark Tag metabolic tag was added to gene: COQ4.
BabyScreen+ newborn screening v0.1687 COLQ Zornitza Stark Tag neurological tag was added to gene: COLQ.
BabyScreen+ newborn screening v0.1687 CASR Zornitza Stark Marked gene: CASR as ready
BabyScreen+ newborn screening v0.1687 CASR Zornitza Stark Gene: casr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1687 CASR Zornitza Stark Phenotypes for gene: CASR were changed from Hyperparathyroidism, neonatal, MIM# 239200 to Hypocalcemia, autosomal dominant MIM#601198; Hyperparathyroidism, neonatal MIM#239200
BabyScreen+ newborn screening v0.1686 CASR Zornitza Stark Mode of inheritance for gene: CASR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1685 CASR Zornitza Stark changed review comment from: AD hypoCa: Established gene-disease association.

Congenital onset.

Treatment: Thiazide diuretics, calcium, calcitriol.

Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium.; to: AD hypoCa: Established gene-disease association.

Congenital onset.

Treatment: Thiazide diuretics, calcium, calcitriol.

Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium.

AD/AR hyperparathyroidism: established gene-disease association.

Congenital onset.

Treatment: bisphosphonate, parathyroidectomy, cinacalcet

Non-genetic confirmatory testing: Ca, PTH.
BabyScreen+ newborn screening v0.1685 CASR Zornitza Stark changed review comment from: Established gene-disease association.

Congenital onset.

Treatment: Thiazide diuretics, calcium, calcitriol.

Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium.; to: AD hypoCa: Established gene-disease association.

Congenital onset.

Treatment: Thiazide diuretics, calcium, calcitriol.

Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium.
BabyScreen+ newborn screening v0.1685 CASR Zornitza Stark edited their review of gene: CASR: Changed phenotypes: Hypocalcemia, autosomal dominant MIM#601198, Hyperparathyroidism, neonatal MIM#239200
BabyScreen+ newborn screening v0.1685 CASR Zornitza Stark edited their review of gene: CASR: Changed phenotypes: Hypocalciuric hypercalcemia, type I, MIM# 145980, Hyperparathyroidism, neonatal MIM#239200
BabyScreen+ newborn screening v0.1685 CASR Zornitza Stark edited their review of gene: CASR: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1685 CASR Zornitza Stark Mode of inheritance for gene: CASR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1684 CASR Zornitza Stark changed review comment from: Treatment: Thiazide diuretics, calcium, calcitriol; to: Established gene-disease association.

Congenital onset.

Treatment: Thiazide diuretics, calcium, calcitriol.

Non-genetic confirmatory testing: parathyroid hormone level, urinary calcium excretion, serum calcium.
BabyScreen+ newborn screening v0.1684 CASR Zornitza Stark edited their review of gene: CASR: Changed phenotypes: Hypocalciuric hypercalcemia, type I, MIM# 145980
BabyScreen+ newborn screening v0.1684 CASR Zornitza Stark reviewed gene: CASR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1684 COL4A3 Zornitza Stark Marked gene: COL4A3 as ready
BabyScreen+ newborn screening v0.1684 COL4A3 Zornitza Stark Gene: col4a3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1684 COL4A3 Zornitza Stark Phenotypes for gene: COL4A3 were changed from Alport syndrome to Alport syndrome 2, autosomal recessive, MIM# 203780
BabyScreen+ newborn screening v0.1683 COL4A3 Zornitza Stark Mode of inheritance for gene: COL4A3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1682 COL4A3 Zornitza Stark Tag treatable tag was added to gene: COL4A3.
Tag renal tag was added to gene: COL4A3.
BabyScreen+ newborn screening v0.1682 COL4A3 Zornitza Stark reviewed gene: COL4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alport syndrome 2, autosomal recessive, MIM# 203780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1682 COL4A4 Zornitza Stark Marked gene: COL4A4 as ready
BabyScreen+ newborn screening v0.1682 COL4A4 Zornitza Stark Gene: col4a4 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1682 COL4A4 Zornitza Stark Phenotypes for gene: COL4A4 were changed from Alport syndrome to Alport syndrome 2, autosomal recessive MIM#203780
BabyScreen+ newborn screening v0.1681 COL4A4 Zornitza Stark Tag treatable tag was added to gene: COL4A4.
Tag renal tag was added to gene: COL4A4.
BabyScreen+ newborn screening v0.1681 COL4A4 Zornitza Stark changed review comment from: Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Individuals with AR AS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria.; to: Well established gene-disease association.

Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Individuals with AR AS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria.
BabyScreen+ newborn screening v0.1681 COL4A4 Zornitza Stark changed review comment from: Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Males with XLAS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria. Guidelines differ slightly for the initiation of treatment in females with XLAS; one guideline recommends initiation of treatment at onset of microalbuminuria while a second recommends initiation at onset of microalbuminuria, hypertension, or renal impairment.; to: Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Individuals with AR AS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria.
BabyScreen+ newborn screening v0.1681 COL4A4 Zornitza Stark edited their review of gene: COL4A4: Changed rating: GREEN; Changed phenotypes: Alport syndrome 2, autosomal recessive MIM#203780; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1681 COL4A4 Zornitza Stark commented on gene: COL4A4
BabyScreen+ newborn screening v0.1681 COL4A5 Zornitza Stark changed review comment from: Well established gene-disease association.

Natural history: In males, truncating variants in COL4A5 are associated with an earlier age at onset of kidney failure; risk of ESRD before age 30 is estimated as 90% for large rearrangements and pathogenic nonsense and frameshift variants, 70% for splice variants, and 50% for missense variants. In males, progressive SNHL is usually present by late childhood or early adolescence, and interior lenticous typically becomes apparent in late adolescence or early adulthood. In females, renal disease ranges from asymptomatic disease to lifelong microhematuria to renal failure at a young age. In females, progressive SNHL is typically later in life, lenticonus may not occur, and central retinopathy is rare.

Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Males with XLAS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria. Guidelines differ slightly for the initiation of treatment in females with XLAS; one guideline recommends initiation of treatment at onset of microalbuminuria while a second recommends initiation at onset of microalbuminuria, hypertension, or renal impairment.

For review: screen both males and females?; to: Well established gene-disease association.

Natural history: In males, truncating variants in COL4A5 are associated with an earlier age at onset of kidney failure; risk of ESRD before age 30 is estimated as 90% for large rearrangements and pathogenic nonsense and frameshift variants, 70% for splice variants, and 50% for missense variants. In males, progressive SNHL is usually present by late childhood or early adolescence, and interior lenticous typically becomes apparent in late adolescence or early adulthood. In females, renal disease ranges from asymptomatic disease to lifelong microhematuria to renal failure at a young age. In females, progressive SNHL is typically later in life, lenticonus may not occur, and central retinopathy is rare.

Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Males with XLAS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria. Guidelines differ slightly for the initiation of treatment in females with XLAS; one guideline recommends initiation of treatment at onset of microalbuminuria while a second recommends initiation at onset of microalbuminuria, hypertension, or renal impairment.
BabyScreen+ newborn screening v0.1681 COL4A5 Zornitza Stark Tag renal tag was added to gene: COL4A5.
BabyScreen+ newborn screening v0.1681 COL3A1 Zornitza Stark Marked gene: COL3A1 as ready
BabyScreen+ newborn screening v0.1681 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1681 COL3A1 Zornitza Stark Phenotypes for gene: COL3A1 were changed from Ehlers-Danlos syndrome, type IV to Ehlers-Danlos syndrome, vascular type, MIM# 130050
BabyScreen+ newborn screening v0.1680 COL3A1 Zornitza Stark Classified gene: COL3A1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1680 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1679 COL3A1 Zornitza Stark Tag for review tag was added to gene: COL3A1.
Tag cardiac tag was added to gene: COL3A1.
BabyScreen+ newborn screening v0.1679 COL3A1 Zornitza Stark reviewed gene: COL3A1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, vascular type, MIM# 130050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1679 COL2A1 Zornitza Stark Tag for review was removed from gene: COL2A1.
Tag treatable tag was added to gene: COL2A1.
Tag ophthalmological tag was added to gene: COL2A1.
BabyScreen+ newborn screening v0.1679 COL1A2 Zornitza Stark Tag treatable tag was added to gene: COL1A2.
Tag skeletal tag was added to gene: COL1A2.
BabyScreen+ newborn screening v0.1679 COL1A1 Zornitza Stark Tag skeletal tag was added to gene: COL1A1.
BabyScreen+ newborn screening v0.1679 COL13A1 Zornitza Stark Tag neurological tag was added to gene: COL13A1.
BabyScreen+ newborn screening v0.1679 COL11A2 Zornitza Stark Tag deafness tag was added to gene: COL11A2.
BabyScreen+ newborn screening v0.1679 COL11A1 Zornitza Stark Tag treatable tag was added to gene: COL11A1.
BabyScreen+ newborn screening v0.1679 COCH Zornitza Stark Tag deafness tag was added to gene: COCH.
BabyScreen+ newborn screening v0.1679 CLPP Zornitza Stark Tag treatable tag was added to gene: CLPP.
Tag metabolic tag was added to gene: CLPP.
BabyScreen+ newborn screening v0.1679 CLDN14 Zornitza Stark Tag deafness tag was added to gene: CLDN14.
BabyScreen+ newborn screening v0.1679 CLCN7 Zornitza Stark Tag skeletal tag was added to gene: CLCN7.
BabyScreen+ newborn screening v0.1679 CIB2 Zornitza Stark Tag deafness tag was added to gene: CIB2.
BabyScreen+ newborn screening v0.1679 CHRNE Zornitza Stark Tag treatable tag was added to gene: CHRNE.
Tag neurological tag was added to gene: CHRNE.
BabyScreen+ newborn screening v0.1679 CHRND Zornitza Stark Tag treatable tag was added to gene: CHRND.
Tag neurological tag was added to gene: CHRND.
BabyScreen+ newborn screening v0.1679 CHRNA1 Zornitza Stark Tag neurological tag was added to gene: CHRNA1.
BabyScreen+ newborn screening v0.1679 CHAT Zornitza Stark Tag neurological tag was added to gene: CHAT.
BabyScreen+ newborn screening v0.1679 CFTR Zornitza Stark Tag respiratory tag was added to gene: CFTR.
BabyScreen+ newborn screening v0.1679 CFP Zornitza Stark Tag treatable tag was added to gene: CFP.
Tag immunological tag was added to gene: CFP.
BabyScreen+ newborn screening v0.1679 CDKN1C Zornitza Stark Marked gene: CDKN1C as ready
BabyScreen+ newborn screening v0.1679 CDKN1C Zornitza Stark Gene: cdkn1c has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1679 CDKN1C Zornitza Stark Phenotypes for gene: CDKN1C were changed from Beckwith-Wiedemann syndrome, MIM#130650 to IMAGe syndrome, MIM# 614732
BabyScreen+ newborn screening v0.1678 CDKN1C Zornitza Stark Mode of inheritance for gene: CDKN1C was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
BabyScreen+ newborn screening v0.1677 CDKN1C Zornitza Stark Tag treatable tag was added to gene: CDKN1C.
Tag endocrine tag was added to gene: CDKN1C.
BabyScreen+ newborn screening v0.1677 CDKN1C Zornitza Stark reviewed gene: CDKN1C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: IMAGe syndrome, MIM# 614732; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
BabyScreen+ newborn screening v0.1677 CDH23 Zornitza Stark Tag deafness tag was added to gene: CDH23.
BabyScreen+ newborn screening v0.1677 CDC14A Zornitza Stark Tag deafness tag was added to gene: CDC14A.
BabyScreen+ newborn screening v0.1677 CDAN1 Zornitza Stark Marked gene: CDAN1 as ready
BabyScreen+ newborn screening v0.1677 CDAN1 Zornitza Stark Gene: cdan1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1677 CDAN1 Zornitza Stark Phenotypes for gene: CDAN1 were changed from Anemia, congenital dyserythropoietic, type I to Dyserythropoietic anaemia, congenital, type Ia, MIM#224120
BabyScreen+ newborn screening v0.1676 CDAN1 Zornitza Stark Classified gene: CDAN1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1676 CDAN1 Zornitza Stark Gene: cdan1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1675 CDAN1 Zornitza Stark reviewed gene: CDAN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyserythropoietic anaemia, congenital, type Ia, 224120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1675 CDAN1 Zornitza Stark Tag treatable tag was added to gene: CDAN1.
Tag haematological tag was added to gene: CDAN1.
BabyScreen+ newborn screening v0.1675 CD79B Zornitza Stark Tag immunological tag was added to gene: CD79B.
BabyScreen+ newborn screening v0.1675 CD79A Zornitza Stark Tag immunological tag was added to gene: CD79A.
BabyScreen+ newborn screening v0.1675 CD40LG Zornitza Stark Tag immunological tag was added to gene: CD40LG.
BabyScreen+ newborn screening v0.1675 CD3E Zornitza Stark Tag treatable tag was added to gene: CD3E.
Tag immunological tag was added to gene: CD3E.
BabyScreen+ newborn screening v0.1675 CD3D Zornitza Stark Tag immunological tag was added to gene: CD3D.
BabyScreen+ newborn screening v0.1675 CAVIN1 Zornitza Stark Tag endocrine tag was added to gene: CAVIN1.
BabyScreen+ newborn screening v0.1675 CASR Zornitza Stark Tag treatable tag was added to gene: CASR.
Tag endocrine tag was added to gene: CASR.
BabyScreen+ newborn screening v0.1675 CARD11 Zornitza Stark Tag treatable tag was added to gene: CARD11.
Tag immunological tag was added to gene: CARD11.
BabyScreen+ newborn screening v0.1675 CABP2 Zornitza Stark Tag deafness tag was added to gene: CABP2.
BabyScreen+ newborn screening v0.1675 CA5A Zornitza Stark Tag metabolic tag was added to gene: CA5A.
BabyScreen+ newborn screening v0.1675 CA2 Zornitza Stark Tag skeletal tag was added to gene: CA2.
BabyScreen+ newborn screening v0.1675 C9 Zornitza Stark Tag immunological tag was added to gene: C9.
BabyScreen+ newborn screening v0.1675 C8B Zornitza Stark Tag treatable tag was added to gene: C8B.
Tag immunological tag was added to gene: C8B.
BabyScreen+ newborn screening v0.1675 C7 Zornitza Stark Tag immunological tag was added to gene: C7.
BabyScreen+ newborn screening v0.1675 C6 Zornitza Stark Tag immunological tag was added to gene: C6.
BabyScreen+ newborn screening v0.1675 C5 Zornitza Stark Tag immunological tag was added to gene: C5.
BabyScreen+ newborn screening v0.1675 GCH1 John Christodoulou reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32456656, PMID: 20301681; Phenotypes: dystonia, truncal hypotonia, peripheral hypertonia, seizures, ID, fever; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1675 UROS John Christodoulou reviewed gene: UROS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30685241; Phenotypes: hydros, photosensitivity, erythrodontia, corneal scarring, haemolytic anaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1675 TRMU John Christodoulou reviewed gene: TRMU: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33485800, PMID: 33365252; Phenotypes: liver failure, Leigh syndrome, cardiomyopathy' myopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1675 TPP1 John Christodoulou reviewed gene: TPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30783219, PMID: 32280231; Phenotypes: neruodegeneration, seizures, loss of vision, loss of language; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1675 BTK Zornitza Stark Tag immunological tag was added to gene: BTK.
BabyScreen+ newborn screening v0.1675 BTD Zornitza Stark Tag metabolic tag was added to gene: BTD.
BabyScreen+ newborn screening v0.1675 BSND Zornitza Stark Tag renal tag was added to gene: BSND.
BabyScreen+ newborn screening v0.1675 BSCL2 Zornitza Stark Tag endocrine tag was added to gene: BSCL2.
BabyScreen+ newborn screening v0.1675 BRIP1 Zornitza Stark Tag haematological tag was added to gene: BRIP1.
BabyScreen+ newborn screening v0.1675 BLNK Zornitza Stark Tag immunological tag was added to gene: BLNK.
BabyScreen+ newborn screening v0.1675 BCKDK Zornitza Stark Tag metabolic tag was added to gene: BCKDK.
BabyScreen+ newborn screening v0.1675 BCKDHB Zornitza Stark Tag metabolic tag was added to gene: BCKDHB.
BabyScreen+ newborn screening v0.1675 BCKDHA Zornitza Stark Tag metabolic tag was added to gene: BCKDHA.
BabyScreen+ newborn screening v0.1675 TFG Zornitza Stark Marked gene: TFG as ready
BabyScreen+ newborn screening v0.1675 TFG Zornitza Stark Gene: tfg has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1675 TFG Zornitza Stark Phenotypes for gene: TFG were changed from Hereditary motor and sensory neuropathy to Hereditary motor and sensory neuropathy, Okinawa type, MIM# 604484; Spastic paraplegia 57, autosomal recessive, MIM# 615658
BabyScreen+ newborn screening v0.1674 TFG Zornitza Stark Mode of inheritance for gene: TFG was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1673 TFG Zornitza Stark Classified gene: TFG as Red List (low evidence)
BabyScreen+ newborn screening v0.1673 TFG Zornitza Stark Gene: tfg has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1672 TFG Zornitza Stark reviewed gene: TFG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary motor and sensory neuropathy, Okinawa type, MIM# 604484, Spastic paraplegia 57, autosomal recessive, MIM# 615658; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1672 TG Zornitza Stark Marked gene: TG as ready
BabyScreen+ newborn screening v0.1672 TG Zornitza Stark Gene: tg has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1672 TG Zornitza Stark Phenotypes for gene: TG were changed from Thyroid dyshormonogenesis 3 to Thyroid dyshormonogenesis 3, MIM# 274700
BabyScreen+ newborn screening v0.1671 TG Zornitza Stark Publications for gene: TG were set to
BabyScreen+ newborn screening v0.1670 TG Zornitza Stark Tag treatable tag was added to gene: TG.
Tag endocrine tag was added to gene: TG.
BabyScreen+ newborn screening v0.1670 TG Zornitza Stark reviewed gene: TG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid dyshormonogenesis 3, MIM# 274700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1670 TGM5 Zornitza Stark Marked gene: TGM5 as ready
BabyScreen+ newborn screening v0.1670 TGM5 Zornitza Stark Gene: tgm5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1670 TGM5 Zornitza Stark Phenotypes for gene: TGM5 were changed from Peeling skin syndrome, acral type to Peeling skin syndrome 2, MIM# 609796
BabyScreen+ newborn screening v0.1669 TGM5 Zornitza Stark Classified gene: TGM5 as Red List (low evidence)
BabyScreen+ newborn screening v0.1669 TGM5 Zornitza Stark Gene: tgm5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1668 TGM5 Zornitza Stark reviewed gene: TGM5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Peeling skin syndrome 2, MIM# 609796; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1668 TGM1 Zornitza Stark Marked gene: TGM1 as ready
BabyScreen+ newborn screening v0.1668 TGM1 Zornitza Stark Gene: tgm1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1668 TGM1 Zornitza Stark Phenotypes for gene: TGM1 were changed from Ichthyosis, congenital, autosomal recessive to Ichthyosis, congenital, autosomal recessive 1 (MIM#242300)
BabyScreen+ newborn screening v0.1667 TGM1 Zornitza Stark Classified gene: TGM1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1667 TGM1 Zornitza Stark Gene: tgm1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1666 TGM1 Zornitza Stark reviewed gene: TGM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 1 (MIM#242300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1666 TGFBR2 Zornitza Stark Marked gene: TGFBR2 as ready
BabyScreen+ newborn screening v0.1666 TGFBR2 Zornitza Stark Gene: tgfbr2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1666 TGFBR2 Zornitza Stark Phenotypes for gene: TGFBR2 were changed from Loeys-Dietz syndrome to Loeys-Dietz syndrome 2, MIM# 610168
BabyScreen+ newborn screening v0.1665 TGFBR2 Zornitza Stark Tag cardiac tag was added to gene: TGFBR2.
Tag treatable tag was added to gene: TGFBR2.
BabyScreen+ newborn screening v0.1665 TGFBR2 Zornitza Stark edited their review of gene: TGFBR2: Changed phenotypes: Loeys-Dietz syndrome 2, MIM# 610168
BabyScreen+ newborn screening v0.1665 TGFBR2 Zornitza Stark reviewed gene: TGFBR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1665 TGFBR1 Zornitza Stark Marked gene: TGFBR1 as ready
BabyScreen+ newborn screening v0.1665 TGFBR1 Zornitza Stark Gene: tgfbr1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1665 TGFBR1 Zornitza Stark Phenotypes for gene: TGFBR1 were changed from Loeys-Dietz syndrome to Loeys-Dietz syndrome 1, MIM# 609192
BabyScreen+ newborn screening v0.1664 TGFBR1 Zornitza Stark Tag cardiac tag was added to gene: TGFBR1.
Tag treatable tag was added to gene: TGFBR1.
BabyScreen+ newborn screening v0.1664 TGFBR1 Zornitza Stark reviewed gene: TGFBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 1, MIM# 609192; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1664 TH Zornitza Stark Marked gene: TH as ready
BabyScreen+ newborn screening v0.1664 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1664 TH Zornitza Stark Publications for gene: TH were set to
BabyScreen+ newborn screening v0.1663 TH Zornitza Stark Tag treatable tag was added to gene: TH.
Tag endocrine tag was added to gene: TH.
BabyScreen+ newborn screening v0.1663 THRA Zornitza Stark Marked gene: THRA as ready
BabyScreen+ newborn screening v0.1663 THRA Zornitza Stark Gene: thra has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1663 THRA Zornitza Stark Phenotypes for gene: THRA were changed from Hypothyroidism, congenital, nongoitrous, 6 to Hypothyroidism, congenital, nongoitrous, 6, MIM# 614450
BabyScreen+ newborn screening v0.1662 THRA Zornitza Stark Publications for gene: THRA were set to
BabyScreen+ newborn screening v0.1661 THRA Zornitza Stark Tag treatable tag was added to gene: THRA.
Tag endocrine tag was added to gene: THRA.
BabyScreen+ newborn screening v0.1661 THRA Zornitza Stark reviewed gene: THRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypothyroidism, congenital, nongoitrous, 6, MIM# 614450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1661 THRB Zornitza Stark Marked gene: THRB as ready
BabyScreen+ newborn screening v0.1661 THRB Zornitza Stark Gene: thrb has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1661 THRB Zornitza Stark Phenotypes for gene: THRB were changed from Thyroid hormone resistance to Thyroid hormone resistance, MIM# 188570; Thyroid hormone resistance, autosomal recessive, MIM# 274300; Thyroid hormone resistance, selective pituitary, MIM# 145650
BabyScreen+ newborn screening v0.1660 THRB Zornitza Stark Mode of inheritance for gene: THRB was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1659 THRB Zornitza Stark Classified gene: THRB as Red List (low evidence)
BabyScreen+ newborn screening v0.1659 THRB Zornitza Stark Gene: thrb has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1658 THRB Zornitza Stark reviewed gene: THRB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid hormone resistance, MIM# 188570, Thyroid hormone resistance, autosomal recessive, MIM# 274300, Thyroid hormone resistance, selective pituitary, MIM# 145650; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1658 TIMM8A Zornitza Stark Marked gene: TIMM8A as ready
BabyScreen+ newborn screening v0.1658 TIMM8A Zornitza Stark Gene: timm8a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1658 TIMM8A Zornitza Stark Phenotypes for gene: TIMM8A were changed from Mohr-Tranebjaerg syndrome to Mohr-Tranebjaerg syndrome MIM#304700
BabyScreen+ newborn screening v0.1657 TIMM8A Zornitza Stark Publications for gene: TIMM8A were set to
BabyScreen+ newborn screening v0.1656 TIMM8A Zornitza Stark Classified gene: TIMM8A as Red List (low evidence)
BabyScreen+ newborn screening v0.1656 TIMM8A Zornitza Stark Gene: timm8a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1655 TK2 Zornitza Stark Publications for gene: TK2 were set to
BabyScreen+ newborn screening v0.1654 TK2 Zornitza Stark Marked gene: TK2 as ready
BabyScreen+ newborn screening v0.1654 TK2 Zornitza Stark Gene: tk2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1654 TK2 Zornitza Stark Phenotypes for gene: TK2 were changed from Mitochondrial DNA depletion syndrome to Mitochondrial DNA depletion syndrome 2 (myopathic type), 609560
BabyScreen+ newborn screening v0.1653 TK2 Zornitza Stark Tag treatable tag was added to gene: TK2.
Tag metabolic tag was added to gene: TK2.
BabyScreen+ newborn screening v0.1653 TMC1 Zornitza Stark Marked gene: TMC1 as ready
BabyScreen+ newborn screening v0.1653 TMC1 Zornitza Stark Gene: tmc1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1653 TMC1 Zornitza Stark Tag deafness tag was added to gene: TMC1.
BabyScreen+ newborn screening v0.1653 TMC1 Zornitza Stark Phenotypes for gene: TMC1 were changed from Deafness to Deafness, autosomal recessive 7 MIM#600974
BabyScreen+ newborn screening v0.1652 TMC1 Zornitza Stark Publications for gene: TMC1 were set to
BabyScreen+ newborn screening v0.1651 TMEM43 Zornitza Stark Marked gene: TMEM43 as ready
BabyScreen+ newborn screening v0.1651 TMEM43 Zornitza Stark Gene: tmem43 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1651 TMEM43 Zornitza Stark Phenotypes for gene: TMEM43 were changed from Arrhythmogenic right ventricular dysplasia 5 to Arrhythmogenic right ventricular dysplasia 5 MIM#604400
BabyScreen+ newborn screening v0.1650 TMEM43 Zornitza Stark Publications for gene: TMEM43 were set to
BabyScreen+ newborn screening v0.1649 TMEM43 Zornitza Stark Classified gene: TMEM43 as Red List (low evidence)
BabyScreen+ newborn screening v0.1649 TMEM43 Zornitza Stark Gene: tmem43 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1648 TMEM67 Zornitza Stark Marked gene: TMEM67 as ready
BabyScreen+ newborn screening v0.1648 TMEM67 Zornitza Stark Gene: tmem67 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1648 TMEM67 Zornitza Stark Phenotypes for gene: TMEM67 were changed from Joubert syndrome; Meckel syndrome to COACH syndrome MIM#216360; Joubert syndrome MIM#10688; Meckel syndrome MIM#607361; Nephronophthisis MIM#613550
BabyScreen+ newborn screening v0.1647 TMEM67 Zornitza Stark Publications for gene: TMEM67 were set to
BabyScreen+ newborn screening v0.1646 TMEM67 Zornitza Stark Classified gene: TMEM67 as Red List (low evidence)
BabyScreen+ newborn screening v0.1646 TMEM67 Zornitza Stark Gene: tmem67 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1645 TMIE Zornitza Stark Marked gene: TMIE as ready
BabyScreen+ newborn screening v0.1645 TMIE Zornitza Stark Gene: tmie has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1645 TK2 John Christodoulou reviewed gene: TK2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29602790, PMID: 31125140, PMID: 23385875; Phenotypes: myopathy, ophthalmoparesis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1645 TMIE Zornitza Stark Phenotypes for gene: TMIE were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 6 MIM#600971
BabyScreen+ newborn screening v0.1644 TMIE Zornitza Stark Publications for gene: TMIE were set to
BabyScreen+ newborn screening v0.1643 TMIE Zornitza Stark Tag deafness tag was added to gene: TMIE.
BabyScreen+ newborn screening v0.1643 TMPRSS3 Zornitza Stark Tag deafness tag was added to gene: TMPRSS3.
BabyScreen+ newborn screening v0.1643 TRIOBP Zornitza Stark Tag deafness tag was added to gene: TRIOBP.
BabyScreen+ newborn screening v0.1643 TRMU Zornitza Stark Tag liver tag was added to gene: TRMU.
BabyScreen+ newborn screening v0.1643 TSHB Zornitza Stark Tag endocrine tag was added to gene: TSHB.
BabyScreen+ newborn screening v0.1643 TTPA Zornitza Stark Tag neurological tag was added to gene: TTPA.
BabyScreen+ newborn screening v0.1643 THRA John Christodoulou changed review comment from: Congenital nongoitrous hypothyroidism 6

normal TSH, so will be missed by NBS

treatment with thyroxine; to: Congenital nongoitrous hypothyroidism 6

normal TSH, so will be missed by NBS

treatment with thyroxine; others report that patients are resistant to thyroxine therapy (PMID: 28527577)
BabyScreen+ newborn screening v0.1643 THRA John Christodoulou edited their review of gene: THRA: Changed rating: AMBER
BabyScreen+ newborn screening v0.1643 THRA John Christodoulou reviewed gene: THRA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33272083, PMID: 32349464; Phenotypes: goitre, macrocephaly, delayed suture closure; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1643 TH John Christodoulou reviewed gene: TH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301610; Phenotypes: dystonia, Parkinsonism, dev delay, hypotonia, oculogyric crises; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1643 UBE2T Zornitza Stark Tag haematological tag was added to gene: UBE2T.
BabyScreen+ newborn screening v0.1643 UGT1A1 Zornitza Stark Tag liver tag was added to gene: UGT1A1.
BabyScreen+ newborn screening v0.1643 UNC13D Zornitza Stark Tag immunological tag was added to gene: UNC13D.
BabyScreen+ newborn screening v0.1643 UROS Zornitza Stark Marked gene: UROS as ready
BabyScreen+ newborn screening v0.1643 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1643 UROS Zornitza Stark Phenotypes for gene: UROS were changed from Porphyria, congenital erythropoietic to Porphyria, congenital erythropoietic MIM#263700
BabyScreen+ newborn screening v0.1642 UROS Zornitza Stark Publications for gene: UROS were set to
BabyScreen+ newborn screening v0.1641 UROS Zornitza Stark Tag treatable tag was added to gene: UROS.
Tag haematological tag was added to gene: UROS.
BabyScreen+ newborn screening v0.1641 USH1C Zornitza Stark Marked gene: USH1C as ready
BabyScreen+ newborn screening v0.1641 USH1C Zornitza Stark Gene: ush1c has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1641 USH1C Zornitza Stark Phenotypes for gene: USH1C were changed from Usher syndrome 1 to Usher syndrome type 1 MIM#276904
BabyScreen+ newborn screening v0.1640 USH1C Zornitza Stark Publications for gene: USH1C were set to
BabyScreen+ newborn screening v0.1639 USH1C Zornitza Stark Tag deafness tag was added to gene: USH1C.
BabyScreen+ newborn screening v0.1639 USH1G Zornitza Stark Marked gene: USH1G as ready
BabyScreen+ newborn screening v0.1639 USH1G Zornitza Stark Gene: ush1g has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1639 USH1G Zornitza Stark Phenotypes for gene: USH1G were changed from Usher syndrome 1 to Usher syndrome type 1 MIM#606943
BabyScreen+ newborn screening v0.1638 USH1G Zornitza Stark Publications for gene: USH1G were set to
BabyScreen+ newborn screening v0.1637 USH1G Zornitza Stark Tag deafness tag was added to gene: USH1G.
BabyScreen+ newborn screening v0.1637 USH2A Zornitza Stark Marked gene: USH2A as ready
BabyScreen+ newborn screening v0.1637 USH2A Zornitza Stark Gene: ush2a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1637 USH2A Zornitza Stark Phenotypes for gene: USH2A were changed from Usher syndrome 2 to Usher Syndrome Type II MIM#276901
BabyScreen+ newborn screening v0.1636 USH2A Zornitza Stark Publications for gene: USH2A were set to
BabyScreen+ newborn screening v0.1635 USH2A Zornitza Stark Tag deafness tag was added to gene: USH2A.
BabyScreen+ newborn screening v0.1635 TG John Christodoulou reviewed gene: TG: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33272083; Phenotypes: goitre; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1635 VCAN Zornitza Stark Marked gene: VCAN as ready
BabyScreen+ newborn screening v0.1635 VCAN Zornitza Stark Gene: vcan has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1635 VCAN Zornitza Stark Phenotypes for gene: VCAN were changed from Wagner syndrome to Wagner syndrome MIM#143200
BabyScreen+ newborn screening v0.1634 VCAN Zornitza Stark Publications for gene: VCAN were set to
BabyScreen+ newborn screening v0.1633 VCAN Zornitza Stark Classified gene: VCAN as Red List (low evidence)
BabyScreen+ newborn screening v0.1633 VCAN Zornitza Stark Gene: vcan has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1632 VCAN Zornitza Stark reviewed gene: VCAN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Wagner syndrome MIM#143200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1632 VDR Zornitza Stark Tag endocrine tag was added to gene: VDR.
BabyScreen+ newborn screening v0.1632 VHL Zornitza Stark Tag cancer tag was added to gene: VHL.
BabyScreen+ newborn screening v0.1632 VPS45 Zornitza Stark Tag immunological tag was added to gene: VPS45.
BabyScreen+ newborn screening v0.1632 WAS Zornitza Stark Tag treatable tag was added to gene: WAS.
Tag haematological tag was added to gene: WAS.
BabyScreen+ newborn screening v0.1632 WHRN Zornitza Stark Tag deafness tag was added to gene: WHRN.
BabyScreen+ newborn screening v0.1632 XIAP Zornitza Stark Tag immunological tag was added to gene: XIAP.
BabyScreen+ newborn screening v0.1632 ZAP70 Zornitza Stark Tag immunological tag was added to gene: ZAP70.
BabyScreen+ newborn screening v0.1632 TCN2 John Christodoulou reviewed gene: TCN2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32841161, PMID: 33685478; Phenotypes: failure to thrive, megaloblastic anaemia, recurrent infections, ID, vomiting, diarrhoea; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1632 SPR John Christodoulou reviewed gene: SPR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28189489, PMID: 32456656; Phenotypes: ID, dystonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1632 SLC25A19 John Christodoulou reviewed gene: SLC25A19: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31095747; Phenotypes: recurrent encephalopathy, basal ganglia necrosis, generalized dystonia, polyneuropathy, ataxia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1632 SLC25A15 John Christodoulou reviewed gene: SLC25A15: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22649802; Phenotypes: dev delay, encephalopathy, seizures, ataxia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1632 SLC25A13 John Christodoulou reviewed gene: SLC25A13: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301360, PMID: 31255436; Phenotypes: neonatal cholestatic jaundice, neuropsychiatric abnormalities, ID, failure to thrive, hepatomegaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1632 AVPR2 Zornitza Stark Tag endocrine tag was added to gene: AVPR2.
BabyScreen+ newborn screening v0.1632 AVP Zornitza Stark Tag endocrine tag was added to gene: AVP.
BabyScreen+ newborn screening v0.1632 ATP7B Zornitza Stark Tag treatable tag was added to gene: ATP7B.
Tag metabolic tag was added to gene: ATP7B.
BabyScreen+ newborn screening v0.1632 ATP7A Zornitza Stark Tag metabolic tag was added to gene: ATP7A.
BabyScreen+ newborn screening v0.1632 ATP6V1B1 Zornitza Stark Tag renal tag was added to gene: ATP6V1B1.
BabyScreen+ newborn screening v0.1632 ATP6V0A4 Zornitza Stark Tag renal tag was added to gene: ATP6V0A4.
BabyScreen+ newborn screening v0.1632 ASS1 Zornitza Stark Tag metabolic tag was added to gene: ASS1.
BabyScreen+ newborn screening v0.1632 ASL Zornitza Stark Tag metabolic tag was added to gene: ASL.
BabyScreen+ newborn screening v0.1632 ARSB Zornitza Stark Tag metabolic tag was added to gene: ARSB.
BabyScreen+ newborn screening v0.1632 ARSA Zornitza Stark Tag metabolic tag was added to gene: ARSA.
BabyScreen+ newborn screening v0.1632 ARPC1B Zornitza Stark Tag immunological tag was added to gene: ARPC1B.
BabyScreen+ newborn screening v0.1632 ARG1 Zornitza Stark Tag metabolic tag was added to gene: ARG1.
BabyScreen+ newborn screening v0.1632 AQP2 Zornitza Stark Tag endocrine tag was added to gene: AQP2.
BabyScreen+ newborn screening v0.1632 AP3B1 Zornitza Stark Tag haematological tag was added to gene: AP3B1.
BabyScreen+ newborn screening v0.1632 ACVRL1 Zornitza Stark Tag treatable tag was added to gene: ACVRL1.
Tag vascular tag was added to gene: ACVRL1.
BabyScreen+ newborn screening v0.1632 PROS1 Zornitza Stark Marked gene: PROS1 as ready
BabyScreen+ newborn screening v0.1632 PROS1 Zornitza Stark Gene: pros1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1632 PROS1 Zornitza Stark Phenotypes for gene: PROS1 were changed from Protein S deficiency to Thrombophilia 5 due to protein S deficiency, autosomal dominant, MIM# 612336; Thrombophilia 5 due to protein S deficiency, autosomal recessive, MIM# 614514
BabyScreen+ newborn screening v0.1631 PROS1 Zornitza Stark Mode of inheritance for gene: PROS1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1630 PROS1 Zornitza Stark Classified gene: PROS1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1630 PROS1 Zornitza Stark Gene: pros1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1629 PROS1 Zornitza Stark reviewed gene: PROS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombophilia 5 due to protein S deficiency, autosomal dominant, MIM# 612336, Thrombophilia 5 due to protein S deficiency, autosomal recessive, MIM# 614514; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1629 PROP1 Zornitza Stark Marked gene: PROP1 as ready
BabyScreen+ newborn screening v0.1629 PROP1 Zornitza Stark Gene: prop1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1629 PROP1 Zornitza Stark Tag treatable tag was added to gene: PROP1.
Tag endocrine tag was added to gene: PROP1.
BabyScreen+ newborn screening v0.1629 PROP1 Zornitza Stark reviewed gene: PROP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 2 (MIM#262600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1629 PROKR2 Zornitza Stark Marked gene: PROKR2 as ready
BabyScreen+ newborn screening v0.1629 PROKR2 Zornitza Stark Gene: prokr2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1629 PROKR2 Zornitza Stark Phenotypes for gene: PROKR2 were changed from Hypogonadotropic hypogonadism to Hypogonadotropic hypogonadism 3 with or without anosmia, MIM# 244200
BabyScreen+ newborn screening v0.1628 PROKR2 Zornitza Stark Mode of inheritance for gene: PROKR2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1627 PROKR2 Zornitza Stark Classified gene: PROKR2 as Red List (low evidence)
BabyScreen+ newborn screening v0.1627 PROKR2 Zornitza Stark Gene: prokr2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1626 PROKR2 Zornitza Stark reviewed gene: PROKR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypogonadotropic hypogonadism 3 with or without anosmia, MIM# 244200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1626 PROC Zornitza Stark Marked gene: PROC as ready
BabyScreen+ newborn screening v0.1626 PROC Zornitza Stark Gene: proc has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1626 PROC Zornitza Stark Phenotypes for gene: PROC were changed from Thrombophilia due to protein C deficiency to Thrombophilia due to protein C deficiency, autosomal dominant (176860); Thrombophilia due to protein C deficiency, autosomal recessive (612304)
BabyScreen+ newborn screening v0.1625 PROC Zornitza Stark Mode of inheritance for gene: PROC was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1624 PROC Zornitza Stark Classified gene: PROC as Red List (low evidence)
BabyScreen+ newborn screening v0.1624 PROC Zornitza Stark Gene: proc has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1623 PROC Zornitza Stark reviewed gene: PROC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombophilia due to protein C deficiency, autosomal dominant (176860), Thrombophilia due to protein C deficiency, autosomal recessive (612304); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1623 PRKDC Zornitza Stark Marked gene: PRKDC as ready
BabyScreen+ newborn screening v0.1623 PRKDC Zornitza Stark Gene: prkdc has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1623 PRKDC Zornitza Stark Tag treatable tag was added to gene: PRKDC.
Tag immunological tag was added to gene: PRKDC.
BabyScreen+ newborn screening v0.1623 PRKDC Zornitza Stark reviewed gene: PRKDC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 26, with or without neurologic abnormalities MIM# 615966; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1623 PRKAR1A Zornitza Stark Marked gene: PRKAR1A as ready
BabyScreen+ newborn screening v0.1623 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1623 PRKAR1A Zornitza Stark Phenotypes for gene: PRKAR1A were changed from Carney complex to Acrodysostosis 1, with or without hormone resistance, MIM# 101800; Carney complex, type 1, MIM# 160980; Myxoma, intracardiac, MIM# 255960; Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489
BabyScreen+ newborn screening v0.1622 PRKAR1A Zornitza Stark Classified gene: PRKAR1A as Red List (low evidence)
BabyScreen+ newborn screening v0.1622 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1621 PRKAR1A Zornitza Stark reviewed gene: PRKAR1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Acrodysostosis 1, with or without hormone resistance, MIM# 101800, Carney complex, type 1, MIM# 160980, Myxoma, intracardiac, MIM# 255960, Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1621 PRF1 Zornitza Stark Marked gene: PRF1 as ready
BabyScreen+ newborn screening v0.1621 PRF1 Zornitza Stark Gene: prf1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1621 PRF1 Zornitza Stark Tag treatable tag was added to gene: PRF1.
Tag immunological tag was added to gene: PRF1.
BabyScreen+ newborn screening v0.1621 PRF1 Zornitza Stark changed review comment from: Treatment: Emapalumab, bone marrow transplant; to: Well established gene-disease association.

Onset is generally in infancy or early childhood.

Treatment: Emapalumab, bone marrow transplant.

Non-genetic confirmatory tests: natural killer cell activity, cytotoxic T lymphocyte activity
BabyScreen+ newborn screening v0.1621 PRF1 Zornitza Stark edited their review of gene: PRF1: Changed phenotypes: Hemophagocytic lymphohistiocytosis, familial, 2 603553
BabyScreen+ newborn screening v0.1621 PRF1 Zornitza Stark reviewed gene: PRF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1621 PNPO Zornitza Stark Marked gene: PNPO as ready
BabyScreen+ newborn screening v0.1621 PNPO Zornitza Stark Gene: pnpo has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1621 PNPO Zornitza Stark Publications for gene: PNPO were set to
BabyScreen+ newborn screening v0.1620 PNPO Zornitza Stark Phenotypes for gene: PNPO were changed from Epileptic encephalopathy, neonatal, MIM#610090 to Pyridoxamine 5'-phosphate oxidase deficiency, MIM# 610090
BabyScreen+ newborn screening v0.1619 PNPO Zornitza Stark Tag treatable tag was added to gene: PNPO.
Tag metabolic tag was added to gene: PNPO.
BabyScreen+ newborn screening v0.1619 PPT1 Zornitza Stark Marked gene: PPT1 as ready
BabyScreen+ newborn screening v0.1619 PPT1 Zornitza Stark Gene: ppt1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1619 PPT1 Zornitza Stark Publications for gene: PPT1 were set to
BabyScreen+ newborn screening v0.1618 PPT1 Zornitza Stark Phenotypes for gene: PPT1 were changed from Neuronal ceroid lipofuscinosis to Ceroid lipofuscinosis, neuronal, 1, MIM# 256730
BabyScreen+ newborn screening v0.1617 PPT1 Zornitza Stark Classified gene: PPT1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1617 PPT1 Zornitza Stark Gene: ppt1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1616 POU4F3 Zornitza Stark Marked gene: POU4F3 as ready
BabyScreen+ newborn screening v0.1616 POU4F3 Zornitza Stark Gene: pou4f3 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1616 POU4F3 Zornitza Stark Phenotypes for gene: POU4F3 were changed from Deafness, autosomal dominant to Deafness, autosomal dominant 15, MIM# 602459
BabyScreen+ newborn screening v0.1615 POU4F3 Zornitza Stark Classified gene: POU4F3 as Red List (low evidence)
BabyScreen+ newborn screening v0.1615 POU4F3 Zornitza Stark Gene: pou4f3 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1614 POU4F3 Zornitza Stark reviewed gene: POU4F3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 15, MIM# 602459; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1614 POU3F4 Zornitza Stark Marked gene: POU3F4 as ready
BabyScreen+ newborn screening v0.1614 POU3F4 Zornitza Stark Gene: pou3f4 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1614 POU3F4 Zornitza Stark Phenotypes for gene: POU3F4 were changed from Deafness, X-linked to Deafness, X-linked 2, MIM#304400
BabyScreen+ newborn screening v0.1613 POU3F4 Zornitza Stark Classified gene: POU3F4 as Red List (low evidence)
BabyScreen+ newborn screening v0.1613 POU3F4 Zornitza Stark Gene: pou3f4 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1612 PYGL John Christodoulou edited their review of gene: PYGL: Changed rating: GREEN
BabyScreen+ newborn screening v0.1612 POU3F4 Zornitza Stark reviewed gene: POU3F4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, X-linked 2, MIM#304400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1612 PYGL John Christodoulou edited their review of gene: PYGL: Changed publications: PMID: 30659246, PMID: 35725468, PMID: 20301760; Changed phenotypes: hepatomegaly, hypoglycaemia, cardiomyopathy, short stature
BabyScreen+ newborn screening v0.1612 POU1F1 Zornitza Stark Marked gene: POU1F1 as ready
BabyScreen+ newborn screening v0.1612 POU1F1 Zornitza Stark Gene: pou1f1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1612 POU1F1 Zornitza Stark Phenotypes for gene: POU1F1 were changed from Pituitary hormone deficiency, MIM#613038 to Pituitary hormone deficiency, combined, 1 MIM# 613038
BabyScreen+ newborn screening v0.1611 POU1F1 Zornitza Stark Mode of inheritance for gene: POU1F1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1610 POU1F1 Zornitza Stark Tag treatable tag was added to gene: POU1F1.
Tag endocrine tag was added to gene: POU1F1.
BabyScreen+ newborn screening v0.1610 POU1F1 Zornitza Stark reviewed gene: POU1F1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 1 MIM# 613038; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1610 PYGL John Christodoulou commented on gene: PYGL: Generally a mild disorder - presenting in early childhood with hepatomegaly due to glycogen storage

some at risk of hypoglycaemia; some may develop muscle cramps or cardiomyopathy

risk of hepatic adenomas - ultrasound surveillance recommended from 5 yrs

treatment cornstarch and high protein diet - growth improves and hypoglycaemia is no longer problem
BabyScreen+ newborn screening v0.1610 PYGL John Christodoulou reviewed gene: PYGL: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: hepatomegaly, hypoglycaemia, cardiomyo; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1610 PORCN Zornitza Stark Marked gene: PORCN as ready
BabyScreen+ newborn screening v0.1610 PORCN Zornitza Stark Gene: porcn has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1610 PORCN Zornitza Stark Phenotypes for gene: PORCN were changed from Focal dermal hypoplasia to Focal dermal hypoplasia, MIM#305600
BabyScreen+ newborn screening v0.1609 PORCN Zornitza Stark Mode of inheritance for gene: PORCN was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.1608 PORCN Zornitza Stark Classified gene: PORCN as Red List (low evidence)
BabyScreen+ newborn screening v0.1608 PORCN Zornitza Stark Gene: porcn has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1607 PORCN Zornitza Stark reviewed gene: PORCN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Focal dermal hypoplasia, MIM#305600; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.1607 PSPH John Christodoulou reviewed gene: PSPH: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29899766; Phenotypes: microcephaly, seizures, hypertonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1607 POR Zornitza Stark Marked gene: POR as ready
BabyScreen+ newborn screening v0.1607 POR Zornitza Stark Gene: por has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1607 POR Zornitza Stark Phenotypes for gene: POR were changed from Disordered steroidogenesis with and without Antley-Bixler syndrome, MIM#201750 to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM#201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase, MIM# 613571
BabyScreen+ newborn screening v0.1606 POR Zornitza Stark Tag treatable tag was added to gene: POR.
Tag endocrine tag was added to gene: POR.
BabyScreen+ newborn screening v0.1606 POR Zornitza Stark edited their review of gene: POR: Changed rating: GREEN
BabyScreen+ newborn screening v0.1606 POR Zornitza Stark reviewed gene: POR: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM#201750, Disordered steroidogenesis due to cytochrome P450 oxidoreductase, MIM# 613571; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1606 PPT1 John Christodoulou reviewed gene: PPT1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 21990111; Phenotypes: neurodegeneration, seizures, ataxia, optic atrophy, retinal abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1606 POMT2 Zornitza Stark Marked gene: POMT2 as ready
BabyScreen+ newborn screening v0.1606 POMT2 Zornitza Stark Gene: pomt2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1606 POMT2 Zornitza Stark Phenotypes for gene: POMT2 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 MIM# 613158
BabyScreen+ newborn screening v0.1605 POMT2 Zornitza Stark Classified gene: POMT2 as Red List (low evidence)
BabyScreen+ newborn screening v0.1605 POMT2 Zornitza Stark Gene: pomt2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1604 POMT2 Zornitza Stark reviewed gene: POMT2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1604 POMGNT1 Zornitza Stark Marked gene: POMGNT1 as ready
BabyScreen+ newborn screening v0.1604 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1604 POMGNT1 Zornitza Stark Phenotypes for gene: POMGNT1 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 MIM#614830; Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 MIM#618135; Retinitis pigmentosa 76, MIM# 617123
BabyScreen+ newborn screening v0.1603 POMGNT1 Zornitza Stark Classified gene: POMGNT1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1603 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1602 POMGNT1 Zornitza Stark reviewed gene: POMGNT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 MIM#614830, Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 MIM#618135, Retinitis pigmentosa 76 617123; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1602 POLH Zornitza Stark Marked gene: POLH as ready
BabyScreen+ newborn screening v0.1602 POLH Zornitza Stark Gene: polh has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1602 POLH Zornitza Stark Phenotypes for gene: POLH were changed from Xeroderma pigmentosum to Xeroderma pigmentosum, variant type, MIM# 278750
BabyScreen+ newborn screening v0.1601 POLH Zornitza Stark Classified gene: POLH as Red List (low evidence)
BabyScreen+ newborn screening v0.1601 POLH Zornitza Stark Gene: polh has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1600 POLH Zornitza Stark reviewed gene: POLH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Xeroderma pigmentosum, variant type, MIM# 278750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1600 POLG Zornitza Stark Marked gene: POLG as ready
BabyScreen+ newborn screening v0.1600 POLG Zornitza Stark Gene: polg has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1600 POLG Zornitza Stark Phenotypes for gene: POLG were changed from POLG-Related Ataxia Neuropathy Spectrum Disorders to Mitochondrial DNA depletion syndrome 4A (Alpers type) MIM#203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type) MIM#613662; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) MIM#607459; Progressive external ophthalmoplegia, autosomal recessive 1 MIM#258450; Progressive external ophthalmoplegia, autosomal dominant 1, MIM# 157640
BabyScreen+ newborn screening v0.1599 POLG Zornitza Stark Publications for gene: POLG were set to
BabyScreen+ newborn screening v0.1598 POLG Zornitza Stark Mode of inheritance for gene: POLG was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1597 POLG Zornitza Stark Classified gene: POLG as Red List (low evidence)
BabyScreen+ newborn screening v0.1597 POLG Zornitza Stark Gene: polg has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1596 POLG Zornitza Stark reviewed gene: POLG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 4A (Alpers type) MIM#203700, Mitochondrial DNA depletion syndrome 4B (MNGIE type) MIM#613662, Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) MIM#607459, Progressive external ophthalmoplegia, autosomal recessive 1 MIM#258450, Progressive external ophthalmoplegia, autosomal dominant 1, MIM# 157640; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1596 POLG John Christodoulou reviewed gene: POLG: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30451971, PMID: 21880868; Phenotypes: seizures, dev delay, hypotonia, liver failure, neurodegeneration, gut pseudo obstruction, peripheral neuropathy, ophthalmoplegia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1596 PNKP Zornitza Stark Marked gene: PNKP as ready
BabyScreen+ newborn screening v0.1596 PNKP Zornitza Stark Gene: pnkp has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1596 PNKP Zornitza Stark Phenotypes for gene: PNKP were changed from Microcephaly - seizures - developmental delay to Ataxia-oculomotor apraxia 4, MIM#616267; Microcephaly, seizures, and developmental delay, MIM#613402
BabyScreen+ newborn screening v0.1595 PNKP Zornitza Stark Publications for gene: PNKP were set to
BabyScreen+ newborn screening v0.1594 PNKP Zornitza Stark Classified gene: PNKP as Red List (low evidence)
BabyScreen+ newborn screening v0.1594 PNKP Zornitza Stark Gene: pnkp has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1593 PNPO John Christodoulou reviewed gene: PNPO: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34769443, PMID: 32888189; Phenotypes: neonatal seizures, ID; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1593 PNKP John Christodoulou reviewed gene: PNKP: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 27125728, PMID: 27066567, PMID: 27232581; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1593 POMT1 Zornitza Stark Marked gene: POMT1 as ready
BabyScreen+ newborn screening v0.1593 POMT1 Zornitza Stark Gene: pomt1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1593 POMT1 Zornitza Stark Phenotypes for gene: POMT1 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1; Walker-Warburg syndrome to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308
BabyScreen+ newborn screening v0.1592 POMT1 Zornitza Stark Classified gene: POMT1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1592 POMT1 Zornitza Stark Gene: pomt1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1591 POMT1 Zornitza Stark reviewed gene: POMT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1591 PQBP1 Zornitza Stark Marked gene: PQBP1 as ready
BabyScreen+ newborn screening v0.1591 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1591 PQBP1 Zornitza Stark Phenotypes for gene: PQBP1 were changed from Mental retardation to Renpenning syndrome, MIM#309500
BabyScreen+ newborn screening v0.1590 PQBP1 Zornitza Stark Classified gene: PQBP1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1590 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1589 PQBP1 Zornitza Stark reviewed gene: PQBP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Renpenning syndrome, MIM#309500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1589 PNKD Zornitza Stark Marked gene: PNKD as ready
BabyScreen+ newborn screening v0.1589 PNKD Zornitza Stark Gene: pnkd has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1589 PNKD Zornitza Stark Phenotypes for gene: PNKD were changed from Paroxysmal nonkinesiogenic dyskinesia to Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800
BabyScreen+ newborn screening v0.1588 PNKD Zornitza Stark Classified gene: PNKD as Red List (low evidence)
BabyScreen+ newborn screening v0.1588 PNKD Zornitza Stark Gene: pnkd has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1587 PNKD Zornitza Stark reviewed gene: PNKD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1587 PMP22 Zornitza Stark Marked gene: PMP22 as ready
BabyScreen+ newborn screening v0.1587 PMP22 Zornitza Stark Gene: pmp22 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1587 PMP22 Zornitza Stark Phenotypes for gene: PMP22 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, type 1A, MIM# 118220; Charcot-Marie-Tooth disease, type 1E, MIM# 118300; Dejerine-Sottas disease, MIM# 145900; Neuropathy, recurrent, with pressure palsies 162500; Roussy-Levy syndrome 180800
BabyScreen+ newborn screening v0.1586 PMP22 Zornitza Stark Classified gene: PMP22 as Red List (low evidence)
BabyScreen+ newborn screening v0.1586 PMP22 Zornitza Stark Gene: pmp22 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1585 PMP22 Zornitza Stark reviewed gene: PMP22: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 1A, MIM# 118220, Charcot-Marie-Tooth disease, type 1E, MIM# 118300, Dejerine-Sottas disease, MIM# 145900, Neuropathy, recurrent, with pressure palsies 162500, Roussy-Levy syndrome 180800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1585 PMM2 Zornitza Stark Marked gene: PMM2 as ready
BabyScreen+ newborn screening v0.1585 PMM2 Zornitza Stark Gene: pmm2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1585 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from Congenital disorder of glycosylation, type Ia to Congenital disorder of glycosylation, type Ia, MIM# 212065
BabyScreen+ newborn screening v0.1584 PMM2 Zornitza Stark Publications for gene: PMM2 were set to
BabyScreen+ newborn screening v0.1583 PMM2 Zornitza Stark Classified gene: PMM2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1583 PMM2 Zornitza Stark Gene: pmm2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1582 PMM2 Zornitza Stark Tag for review tag was added to gene: PMM2.
Tag metabolic tag was added to gene: PMM2.
BabyScreen+ newborn screening v0.1582 PMM2 Zornitza Stark edited their review of gene: PMM2: Changed rating: AMBER
BabyScreen+ newborn screening v0.1582 PMM2 Zornitza Stark reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30740725, 31636082; Phenotypes: Congenital disorder of glycosylation, type Ia, MIM# 212065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1582 PLPBP Zornitza Stark Marked gene: PLPBP as ready
BabyScreen+ newborn screening v0.1582 PLPBP Zornitza Stark Gene: plpbp has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1582 PLPBP Zornitza Stark Publications for gene: PLPBP were set to
BabyScreen+ newborn screening v0.1581 PLPBP Zornitza Stark Tag treatable tag was added to gene: PLPBP.
Tag metabolic tag was added to gene: PLPBP.
BabyScreen+ newborn screening v0.1581 PLPBP Zornitza Stark reviewed gene: PLPBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 30668673; Phenotypes: Epilepsy, early-onset, vitamin B6-dependent, MIM#617290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1581 PLP1 Zornitza Stark Marked gene: PLP1 as ready
BabyScreen+ newborn screening v0.1581 PLP1 Zornitza Stark Gene: plp1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1581 PLP1 Zornitza Stark Phenotypes for gene: PLP1 were changed from Pelizaeus-Merzbacher disease; Spastic paraplegia 2, X-linked to Pelizaeus-Merzbacher disease MIM#312080; Spastic paraplegia 2, X-linked MIM#312920
BabyScreen+ newborn screening v0.1580 PLP1 Zornitza Stark Classified gene: PLP1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1580 PLP1 Zornitza Stark Gene: plp1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1579 PLP1 Zornitza Stark reviewed gene: PLP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pelizaeus-Merzbacher disease MIM#312080, Spastic paraplegia 2, X-linked MIM#312920; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1579 PLOD1 Zornitza Stark Marked gene: PLOD1 as ready
BabyScreen+ newborn screening v0.1579 PLOD1 Zornitza Stark Gene: plod1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1579 PLOD1 Zornitza Stark Phenotypes for gene: PLOD1 were changed from Ehlers-Danlos syndrome, kyphoscoliotic type to Ehlers-Danlos syndrome, kyphoscoliotic type, MIM# 225400
BabyScreen+ newborn screening v0.1578 PLOD1 Zornitza Stark Classified gene: PLOD1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1578 PLOD1 Zornitza Stark Gene: plod1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1577 PLOD1 Zornitza Stark reviewed gene: PLOD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, kyphoscoliotic type, MIM# 225400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1577 PLG Zornitza Stark Marked gene: PLG as ready
BabyScreen+ newborn screening v0.1577 PLG Zornitza Stark Gene: plg has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1577 PLG Zornitza Stark Phenotypes for gene: PLG were changed from Hereditary angioedema-4 (HAE4), MIM#619360; Plasminogen deficiency, type I, MIM# 217090 to Plasminogen deficiency, type I, MIM# 217090
BabyScreen+ newborn screening v0.1576 PLG Zornitza Stark Tag treatable tag was added to gene: PLG.
Tag haematological tag was added to gene: PLG.
BabyScreen+ newborn screening v0.1576 PLG Zornitza Stark reviewed gene: PLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 29321155; Phenotypes: Plasminogen deficiency, type I, MIM# 217090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1576 PLEC Zornitza Stark Marked gene: PLEC as ready
BabyScreen+ newborn screening v0.1576 PLEC Zornitza Stark Gene: plec has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1576 PLEC Zornitza Stark Phenotypes for gene: PLEC were changed from Muscular dystrophy; Epidermolysis bullosa simplex to Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670; Epidermolysis bullosa simplex with pyloric atresia, MIM# 612138; Epidermolysis bullosa simplex, Ogna type MIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723
BabyScreen+ newborn screening v0.1575 PLEC Zornitza Stark Mode of inheritance for gene: PLEC was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1574 PLEC Zornitza Stark Classified gene: PLEC as Red List (low evidence)
BabyScreen+ newborn screening v0.1574 PLEC Zornitza Stark Gene: plec has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1573 PLEC Zornitza Stark reviewed gene: PLEC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670, Epidermolysis bullosa simplex with pyloric atresia, MIM# 612138, Epidermolysis bullosa simplex, Ogna type MIM#131950, Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1573 PLCE1 Zornitza Stark Marked gene: PLCE1 as ready
BabyScreen+ newborn screening v0.1573 PLCE1 Zornitza Stark Gene: plce1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1573 PLCE1 Zornitza Stark Phenotypes for gene: PLCE1 were changed from Nephrotic syndrome to Nephrotic syndrome, type 3, MIM# 610725
BabyScreen+ newborn screening v0.1572 PLCE1 Zornitza Stark Classified gene: PLCE1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1572 PLCE1 Zornitza Stark Gene: plce1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1571 PLCE1 Zornitza Stark reviewed gene: PLCE1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephrotic syndrome, type 3, MIM# 610725; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1571 PLA2G6 Zornitza Stark Marked gene: PLA2G6 as ready
BabyScreen+ newborn screening v0.1571 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1571 PLA2G6 Zornitza Stark Phenotypes for gene: PLA2G6 were changed from Infantile neuroaxonal dystrophy 1 to Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217; Parkinson disease 14, autosomal recessive MIM#612953
BabyScreen+ newborn screening v0.1570 PLA2G6 Zornitza Stark Classified gene: PLA2G6 as Red List (low evidence)
BabyScreen+ newborn screening v0.1570 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1569 PLA2G6 Zornitza Stark reviewed gene: PLA2G6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Infantile neuroaxonal dystrophy 1 MIM#256600, Neurodegeneration with brain iron accumulation 2B MIM#610217, Parkinson disease 14, autosomal recessive MIM#612953; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1569 PKLR Zornitza Stark Marked gene: PKLR as ready
BabyScreen+ newborn screening v0.1569 PKLR Zornitza Stark Gene: pklr has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1569 PKLR Zornitza Stark Publications for gene: PKLR were set to
BabyScreen+ newborn screening v0.1568 PKLR Zornitza Stark edited their review of gene: PKLR: Changed publications: 32702739
BabyScreen+ newborn screening v0.1568 PKLR Zornitza Stark changed review comment from: ranging from fetal hydrops and symptomatic anemia requiring lifelong transfusions to fully compensated hemolysis.; to: Established gene-disease association.

Severity ranges from fetal hydrops and symptomatic anaemia requiring lifelong transfusions to fully compensated haemolysis.

Treatment: Mitapivat. Red cell transfusions.

For review.
BabyScreen+ newborn screening v0.1568 PKLR Zornitza Stark edited their review of gene: PKLR: Changed phenotypes: Pyruvate Kinase deficiency, MIM# 266200; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1568 PKLR Zornitza Stark reviewed gene: PKLR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
BabyScreen+ newborn screening v0.1568 PKHD1 Zornitza Stark Marked gene: PKHD1 as ready
BabyScreen+ newborn screening v0.1568 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1568 PKHD1 Zornitza Stark Phenotypes for gene: PKHD1 were changed from Polycystic kidney and hepatic disease to Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200
BabyScreen+ newborn screening v0.1567 PKHD1 Zornitza Stark Classified gene: PKHD1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1567 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1566 PKHD1 Zornitza Stark reviewed gene: PKHD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1566 PKD2 Zornitza Stark Marked gene: PKD2 as ready
BabyScreen+ newborn screening v0.1566 PKD2 Zornitza Stark Gene: pkd2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1566 PKD2 Zornitza Stark Phenotypes for gene: PKD2 were changed from Polycystic kidney disease to Polycystic kidney disease 2, MIM# 613095
BabyScreen+ newborn screening v0.1565 PKD2 Zornitza Stark Classified gene: PKD2 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1565 PKD2 Zornitza Stark Gene: pkd2 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1564 PKD2 Zornitza Stark Tag for review tag was added to gene: PKD2.
Tag treatable tag was added to gene: PKD2.
Tag renal tag was added to gene: PKD2.
BabyScreen+ newborn screening v0.1564 PKD2 Zornitza Stark changed review comment from: Well established gene-disease association.

Onset of renal failure is generally in adulthood, though cysts are apparent earlier.

Treatment: Tolvaptan; to: Well established gene-disease association.

Onset of renal failure is generally in late adulthood, though cysts are apparent earlier.

Treatment: Tolvaptan
BabyScreen+ newborn screening v0.1564 PKD2 Zornitza Stark edited their review of gene: PKD2: Changed phenotypes: Polycystic kidney disease 2, MIM# 613095
BabyScreen+ newborn screening v0.1564 PKD2 Zornitza Stark reviewed gene: PKD2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1564 PKD1 Zornitza Stark Marked gene: PKD1 as ready
BabyScreen+ newborn screening v0.1564 PKD1 Zornitza Stark Gene: pkd1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1564 PKD1 Zornitza Stark Phenotypes for gene: PKD1 were changed from Polycystic kidney disease to Polycystic kidney disease 1, MIM# 173900
BabyScreen+ newborn screening v0.1563 PKD1 Zornitza Stark Classified gene: PKD1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1563 PKD1 Zornitza Stark Gene: pkd1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1562 PKD1 Zornitza Stark Tag for review tag was added to gene: PKD1.
Tag treatable tag was added to gene: PKD1.
Tag renal tag was added to gene: PKD1.
BabyScreen+ newborn screening v0.1562 PKD1 Zornitza Stark reviewed gene: PKD1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 1, MIM# 173900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1562 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
BabyScreen+ newborn screening v0.1562 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1562 PIK3CA Zornitza Stark Classified gene: PIK3CA as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1562 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1561 PIK3CA Zornitza Stark Tag for review tag was added to gene: PIK3CA.
BabyScreen+ newborn screening v0.1561 PIK3CA Zornitza Stark gene: PIK3CA was added
gene: PIK3CA was added to gNBS. Sources: Expert list
Mode of inheritance for gene: PIK3CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3CA were set to 33392635; 33639990
Phenotypes for gene: PIK3CA were set to PIK3CA related overgrowth spectrum
Review for gene: PIK3CA was set to AMBER
Added comment: Established association with a range of overgrowth phenotypes.

Note variants are SOMATIC and may not be detectable reliably.

Treatment: alpelisib, miransertib. Unsure if these are available.
Sources: Expert list
BabyScreen+ newborn screening v0.1560 PINK1 Zornitza Stark Marked gene: PINK1 as ready
BabyScreen+ newborn screening v0.1560 PINK1 Zornitza Stark Gene: pink1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1560 PINK1 Zornitza Stark Phenotypes for gene: PINK1 were changed from Parkinson disease 6, early onset to Parkinson disease 6, early onset, MIM#605909
BabyScreen+ newborn screening v0.1559 PINK1 Zornitza Stark Mode of inheritance for gene: PINK1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1558 PINK1 Zornitza Stark Classified gene: PINK1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1558 PINK1 Zornitza Stark Gene: pink1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1557 PINK1 Zornitza Stark reviewed gene: PINK1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Parkinson disease 6, early onset, MIM#605909; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1557 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
BabyScreen+ newborn screening v0.1557 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1557 PIK3R1 Zornitza Stark Publications for gene: PIK3R1 were set to
BabyScreen+ newborn screening v0.1556 PIK3R1 Zornitza Stark Tag treatable tag was added to gene: PIK3R1.
Tag immunological tag was added to gene: PIK3R1.
BabyScreen+ newborn screening v0.1556 PIK3R1 Zornitza Stark reviewed gene: PIK3R1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31111319, 33401995, 34033842; Phenotypes: Immunodeficiency 36, MIM# 616005, Agammaglobulinemia 7, autosomal recessive , MIM# 615214; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1556 PIK3CD Zornitza Stark edited their review of gene: PIK3CD: Changed publications: 30040974, 30336224, 29180244, 16984281, 24136356, 24165795, 24610295, 30911953, 31111319, 34033842
BabyScreen+ newborn screening v0.1556 PIK3CD Zornitza Stark Marked gene: PIK3CD as ready
BabyScreen+ newborn screening v0.1556 PIK3CD Zornitza Stark Gene: pik3cd has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1556 PIK3CD Zornitza Stark Phenotypes for gene: PIK3CD were changed from Immunodeficiency 14, MIM # 615513 to Immunodeficiency 14B, autosomal recessive, MIM# 619281; Immunodeficiency 14A, autosomal dominant, MIM# 615513
BabyScreen+ newborn screening v0.1555 PIK3CD Zornitza Stark Publications for gene: PIK3CD were set to
BabyScreen+ newborn screening v0.1554 PIK3CD Zornitza Stark Mode of inheritance for gene: PIK3CD was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1553 PIK3CD Zornitza Stark Tag treatable tag was added to gene: PIK3CD.
Tag immunological tag was added to gene: PIK3CD.
BabyScreen+ newborn screening v0.1553 PIK3CD Zornitza Stark reviewed gene: PIK3CD: Rating: GREEN; Mode of pathogenicity: None; Publications: 30040974, 30336224, 29180244, 16984281, 24136356, 24165795, 24610295; Phenotypes: Immunodeficiency 14B, autosomal recessive, MIM# 619281, Immunodeficiency 14A, autosomal dominant, MIM# 615513; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1553 PIEZO2 Zornitza Stark Marked gene: PIEZO2 as ready
BabyScreen+ newborn screening v0.1553 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1553 PIEZO2 Zornitza Stark Phenotypes for gene: PIEZO2 were changed from Arthrogryposis, distal, type 5 to Marden-Walker syndrome (MIM#248700); Arthrogryposis, distal, type 3 (MIM#114300); Arthrogryposis, distal, type 5 (MIM#108145); Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146
BabyScreen+ newborn screening v0.1552 PIEZO2 Zornitza Stark Mode of inheritance for gene: PIEZO2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1551 PIEZO2 Zornitza Stark Classified gene: PIEZO2 as Red List (low evidence)
BabyScreen+ newborn screening v0.1551 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1550 PIEZO2 Zornitza Stark reviewed gene: PIEZO2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Marden-Walker syndrome (MIM#248700), Arthrogryposis, distal, type 3 (MIM#114300), Arthrogryposis, distal, type 5 (MIM#108145), Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1550 PDZD7 Zornitza Stark Marked gene: PDZD7 as ready
BabyScreen+ newborn screening v0.1550 PDZD7 Zornitza Stark Gene: pdzd7 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1550 PDZD7 Zornitza Stark Phenotypes for gene: PDZD7 were changed from Usher syndrome to Deafness, autosomal recessive 57, MIM# 618003; Usher syndrome, type IIC, GPR98/PDZD7 digenic, MIM# 605472
BabyScreen+ newborn screening v0.1549 PDZD7 Zornitza Stark reviewed gene: PDZD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 57, MIM# 618003, Usher syndrome, type IIC, GPR98/PDZD7 digenic, MIM# 605472; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1549 PHF6 Zornitza Stark Marked gene: PHF6 as ready
BabyScreen+ newborn screening v0.1549 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1549 PHF6 Zornitza Stark edited their review of gene: PHF6: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1549 PHF6 Zornitza Stark Phenotypes for gene: PHF6 were changed from Borjeson-Forssman-Lehmann syndrome to Borjeson-Forssman-Lehmann syndrome, MIM# 301900
BabyScreen+ newborn screening v0.1548 PHF6 Zornitza Stark Classified gene: PHF6 as Red List (low evidence)
BabyScreen+ newborn screening v0.1548 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1547 PHF6 Zornitza Stark reviewed gene: PHF6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Borjeson-Forssman-Lehmann syndrome, MIM# 301900; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.1547 PHEX Zornitza Stark Marked gene: PHEX as ready
BabyScreen+ newborn screening v0.1547 PHEX Zornitza Stark Gene: phex has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1547 PHEX Zornitza Stark Publications for gene: PHEX were set to
BabyScreen+ newborn screening v0.1546 PHEX Zornitza Stark Mode of inheritance for gene: PHEX was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.1545 PHEX Zornitza Stark Tag treatable tag was added to gene: PHEX.
Tag skeletal tag was added to gene: PHEX.
BabyScreen+ newborn screening v0.1545 PHEX Zornitza Stark reviewed gene: PHEX: Rating: GREEN; Mode of pathogenicity: None; Publications: 29791829; Phenotypes: Hypophosphatemic rickets, MIM#307800; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
BabyScreen+ newborn screening v0.1545 PGM3 Zornitza Stark Marked gene: PGM3 as ready
BabyScreen+ newborn screening v0.1545 PGM3 Zornitza Stark Gene: pgm3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1545 PGM3 Zornitza Stark Tag treatable tag was added to gene: PGM3.
Tag immunological tag was added to gene: PGM3.
BabyScreen+ newborn screening v0.1545 PGM3 Zornitza Stark reviewed gene: PGM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 23, MIM# 615816; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1545 TCOF1 Seb Lunke Marked gene: TCOF1 as ready
BabyScreen+ newborn screening v0.1545 TCOF1 Seb Lunke Gene: tcof1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1545 TCOF1 Seb Lunke Phenotypes for gene: TCOF1 were changed from Treacher Collins syndrome 1 to Treacher Collins syndrome 1, MIM# 154500
BabyScreen+ newborn screening v0.1544 TCOF1 Seb Lunke Classified gene: TCOF1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1544 TCOF1 Seb Lunke Gene: tcof1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1543 TCOF1 Seb Lunke reviewed gene: TCOF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Treacher Collins syndrome 1, MIM# 154500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1543 TCN2 Seb Lunke Marked gene: TCN2 as ready
BabyScreen+ newborn screening v0.1543 TCN2 Seb Lunke Gene: tcn2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1543 TCN2 Seb Lunke Phenotypes for gene: TCN2 were changed from Transcobalamin II deficiency, 275350 to Transcobalamin II deficiency MIM# 275350
BabyScreen+ newborn screening v0.1542 TCN2 Seb Lunke reviewed gene: TCN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Transcobalamin II deficiency MIM# 275350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1542 TCIRG1 Seb Lunke Marked gene: TCIRG1 as ready
BabyScreen+ newborn screening v0.1542 TCIRG1 Seb Lunke Gene: tcirg1 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1542 TCIRG1 Seb Lunke Phenotypes for gene: TCIRG1 were changed from Osteopetrosis, infantile malignant to Osteopetrosis, autosomal recessive 1, MIM# 259700
BabyScreen+ newborn screening v0.1541 TCIRG1 Seb Lunke reviewed gene: TCIRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 1, MIM# 259700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1541 TCF3 Seb Lunke Marked gene: TCF3 as ready
BabyScreen+ newborn screening v0.1541 TCF3 Seb Lunke Gene: tcf3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1541 TCF3 Seb Lunke Phenotypes for gene: TCF3 were changed from Agammaglobulinaemia 8, autosomal dominant, MIM# 616941 to Agammaglobulinaemia 8, autosomal dominant, MIM# 616941; Agammaglobulinaemia 8B, autosomal recessive, MIM# 619824
BabyScreen+ newborn screening v0.1540 TCF3 Seb Lunke Mode of inheritance for gene: TCF3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1539 TCF3 Seb Lunke reviewed gene: TCF3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Agammaglobulinaemia 8, autosomal dominant, MIM# 616941, Agammaglobulinaemia 8B, autosomal recessive, MIM# 619824; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1539 TBX5 Seb Lunke Marked gene: TBX5 as ready
BabyScreen+ newborn screening v0.1539 TBX5 Seb Lunke Gene: tbx5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1539 TBX5 Seb Lunke Phenotypes for gene: TBX5 were changed from Holt-Oram syndrome to Holt-Oram syndrome, MIM# 142900
BabyScreen+ newborn screening v0.1538 TBX5 Seb Lunke Classified gene: TBX5 as Red List (low evidence)
BabyScreen+ newborn screening v0.1538 TBX5 Seb Lunke Gene: tbx5 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1537 TBX5 Seb Lunke reviewed gene: TBX5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Holt-Oram syndrome, MIM# 142900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1537 TBX19 Seb Lunke Marked gene: TBX19 as ready
BabyScreen+ newborn screening v0.1537 TBX19 Seb Lunke Gene: tbx19 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1537 TBX19 Seb Lunke Publications for gene: TBX19 were set to
BabyScreen+ newborn screening v0.1536 TBX19 Seb Lunke Tag treatable tag was added to gene: TBX19.
Tag endocrine tag was added to gene: TBX19.
BabyScreen+ newborn screening v0.1536 TBX19 Seb Lunke reviewed gene: TBX19: Rating: GREEN; Mode of pathogenicity: None; Publications: 30086867; Phenotypes: Adrenocorticotropic hormone deficiency, 201400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1536 TBX1 Seb Lunke Marked gene: TBX1 as ready
BabyScreen+ newborn screening v0.1536 TBX1 Seb Lunke Gene: tbx1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1536 TBX1 Seb Lunke Phenotypes for gene: TBX1 were changed from DiGeorge syndrome to DiGeorge syndrome MIM# 188400; Velocardiofacial syndrome MIM# 192430
BabyScreen+ newborn screening v0.1535 TBX1 Seb Lunke Classified gene: TBX1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1535 TBX1 Seb Lunke Gene: tbx1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1534 TBX1 Seb Lunke Tag for review tag was added to gene: TBX1.
Tag cardiac tag was added to gene: TBX1.
Tag immunological tag was added to gene: TBX1.
BabyScreen+ newborn screening v0.1534 TBX1 Seb Lunke reviewed gene: TBX1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: DiGeorge syndrome MIM# 188400, Velocardiofacial syndrome MIM# 192430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1534 TBC1D24 Seb Lunke Marked gene: TBC1D24 as ready
BabyScreen+ newborn screening v0.1534 TBC1D24 Seb Lunke Gene: tbc1d24 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1534 TBC1D24 Seb Lunke Phenotypes for gene: TBC1D24 were changed from Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndrome to DOORS syndrome MIM#220500
BabyScreen+ newborn screening v0.1533 TBC1D24 Seb Lunke Classified gene: TBC1D24 as Red List (low evidence)
BabyScreen+ newborn screening v0.1533 TBC1D24 Seb Lunke Gene: tbc1d24 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1532 TBC1D24 Seb Lunke reviewed gene: TBC1D24: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: DOORS syndrome MIM#220500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1532 TAZ Seb Lunke Marked gene: TAZ as ready
BabyScreen+ newborn screening v0.1532 TAZ Seb Lunke Gene: taz has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1532 TAZ Seb Lunke Publications for gene: TAZ were set to
BabyScreen+ newborn screening v0.1531 TAZ Seb Lunke reviewed gene: TAZ: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Barth syndrome, MIM# 302060; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1531 TAZ Seb Lunke Deleted their review
BabyScreen+ newborn screening v0.1531 TAZ Seb Lunke Classified gene: TAZ as Red List (low evidence)
BabyScreen+ newborn screening v0.1531 TAZ Seb Lunke Gene: taz has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1530 TAZ Seb Lunke reviewed gene: TAZ: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Barth syndrome, MIM# 302060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1530 TIMM8A Lilian Downie reviewed gene: TIMM8A: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 20301395; Phenotypes: Mohr-Tranebjaerg syndrome MIM#304700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1530 TK2 Lilian Downie reviewed gene: TK2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 23230576, PMID: 29602790, PMID: 31125140; Phenotypes: Mitochondrial DNA depletion syndrome 2 (myopathic type) MIM#609560; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1530 SURF1 Seb Lunke Marked gene: SURF1 as ready
BabyScreen+ newborn screening v0.1530 SURF1 Seb Lunke Gene: surf1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1530 SURF1 Seb Lunke Phenotypes for gene: SURF1 were changed from Leigh syndrome, due to COX deficiency to Charcot-Marie-Tooth disease, type 4K MIM#616684; Mitochondrial complex IV deficiency, nuclear type 1 MIM#220110
BabyScreen+ newborn screening v0.1529 SURF1 Seb Lunke Classified gene: SURF1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1529 SURF1 Seb Lunke Gene: surf1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1528 SURF1 Seb Lunke reviewed gene: SURF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 4K MIM#616684, Mitochondrial complex IV deficiency, nuclear type 1 MIM#220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1528 SUOX Seb Lunke Marked gene: SUOX as ready
BabyScreen+ newborn screening v0.1528 SUOX Seb Lunke Gene: suox has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1528 SUOX Seb Lunke Phenotypes for gene: SUOX were changed from Sulphite oxidase deficiency to Sulfite oxidase deficiency, MIM# 272300
BabyScreen+ newborn screening v0.1527 SUOX Seb Lunke Tag for review tag was added to gene: SUOX.
Tag metabolic tag was added to gene: SUOX.
BabyScreen+ newborn screening v0.1527 SUOX Seb Lunke Classified gene: SUOX as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1527 SUOX Seb Lunke Gene: suox has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1526 SUOX Seb Lunke reviewed gene: SUOX: Rating: AMBER; Mode of pathogenicity: None; Publications: 28933809; Phenotypes: Sulfite oxidase deficiency, MIM# 272300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1526 SUCLG1 Seb Lunke Marked gene: SUCLG1 as ready
BabyScreen+ newborn screening v0.1526 SUCLG1 Seb Lunke Gene: suclg1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1526 SUCLG1 Seb Lunke Phenotypes for gene: SUCLG1 were changed from Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) to Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400
BabyScreen+ newborn screening v0.1525 SUCLG1 Seb Lunke Classified gene: SUCLG1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1525 SUCLG1 Seb Lunke Gene: suclg1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1524 SUCLG1 Seb Lunke reviewed gene: SUCLG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1524 SUCLA2 Seb Lunke Marked gene: SUCLA2 as ready
BabyScreen+ newborn screening v0.1524 SUCLA2 Seb Lunke Gene: sucla2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1524 SUCLA2 Seb Lunke Phenotypes for gene: SUCLA2 were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with methylmalonic aciduria) to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), MIM# 612073, MONDO:0012791
BabyScreen+ newborn screening v0.1523 SUCLA2 Seb Lunke Classified gene: SUCLA2 as Red List (low evidence)
BabyScreen+ newborn screening v0.1523 SUCLA2 Seb Lunke Gene: sucla2 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1522 SUCLA2 Seb Lunke reviewed gene: SUCLA2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), MIM# 612073, MONDO:0012791; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1522 STXBP2 Seb Lunke Marked gene: STXBP2 as ready
BabyScreen+ newborn screening v0.1522 STXBP2 Seb Lunke Gene: stxbp2 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1522 STXBP2 Seb Lunke Phenotypes for gene: STXBP2 were changed from Haemophagocytic lymphohistiocytosis, MIM#613101 to Hemophagocytic lymphohistiocytosis, familial, 5, MIM# 613101
BabyScreen+ newborn screening v0.1521 STXBP2 Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset, multi-system disorder

Treatment: Emapalumab ,Hematopoietic stem cell transplantation (HSCT) - bone marrow transplant

Non-genetic confirmatory test: natural killer cell activity, cytotoxic T lymphocyte activity; to: Established gene-disease association.

Childhood onset, hyperinflammatory disorder

Treatment: Emapalumab ,Hematopoietic stem cell transplantation (HSCT) - bone marrow transplant

Non-genetic confirmatory test: natural killer cell activity, cytotoxic T lymphocyte activity
BabyScreen+ newborn screening v0.1521 STXBP2 Seb Lunke reviewed gene: STXBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemophagocytic lymphohistiocytosis, familial, 5, MIM# 613101; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1521 STXBP1 Seb Lunke Marked gene: STXBP1 as ready
BabyScreen+ newborn screening v0.1521 STXBP1 Seb Lunke Gene: stxbp1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1521 STXBP1 Seb Lunke Phenotypes for gene: STXBP1 were changed from Epileptic encephalopathy, early infantile to Developmental and epileptic encephalopathy 4, MIM# 612164
BabyScreen+ newborn screening v0.1520 STXBP1 Seb Lunke Classified gene: STXBP1 as Red List (low evidence)
BabyScreen+ newborn screening v0.1520 STXBP1 Seb Lunke Gene: stxbp1 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1519 STXBP1 Seb Lunke reviewed gene: STXBP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1519 STXBP1 Seb Lunke Deleted their review
BabyScreen+ newborn screening v0.1519 STXBP1 Seb Lunke Deleted their comment
BabyScreen+ newborn screening v0.1519 STXBP1 Seb Lunke reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1519 STX11 Seb Lunke Marked gene: STX11 as ready
BabyScreen+ newborn screening v0.1519 STX11 Seb Lunke Gene: stx11 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1519 STX11 Seb Lunke reviewed gene: STX11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Haemophagocytic lymphohistiocytosis, familial, 4 , MIM#603552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1519 STS Seb Lunke Marked gene: STS as ready
BabyScreen+ newborn screening v0.1519 STS Seb Lunke Gene: sts has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1519 STS Seb Lunke Phenotypes for gene: STS were changed from Ichthyosis, X-linked to Ichthyosis, X-linked, MIM# 308100
BabyScreen+ newborn screening v0.1518 STS Seb Lunke Classified gene: STS as Red List (low evidence)
BabyScreen+ newborn screening v0.1518 STS Seb Lunke Gene: sts has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1517 STS Seb Lunke reviewed gene: STS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, X-linked, MIM# 308100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
BabyScreen+ newborn screening v0.1517 TMC1 Lilian Downie reviewed gene: TMC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:11850618, PMID: 26879195; Phenotypes: Deafness, autosomal recessive 7 MIM#600974; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1517 TMEM43 Lilian Downie reviewed gene: TMEM43: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301310, PMID: 34674311; Phenotypes: Arrhythmogenic right ventricular dysplasia 5 MIM#604400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1517 STRC Seb Lunke Marked gene: STRC as ready
BabyScreen+ newborn screening v0.1517 STRC Seb Lunke Gene: strc has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1517 STRC Seb Lunke Tag for review tag was added to gene: STRC.
BabyScreen+ newborn screening v0.1517 STRC Seb Lunke Phenotypes for gene: STRC were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 16, MIM# 603720
BabyScreen+ newborn screening v0.1516 STRC Seb Lunke Classified gene: STRC as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1516 STRC Seb Lunke Gene: strc has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1515 STRC Seb Lunke reviewed gene: STRC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 16, MIM# 603720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1515 STRA6 Seb Lunke Marked gene: STRA6 as ready
BabyScreen+ newborn screening v0.1515 STRA6 Seb Lunke Gene: stra6 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1515 STRA6 Seb Lunke Phenotypes for gene: STRA6 were changed from Microphthalmia, syndromic to Microphthalmia, syndromic 9, MIM# 601186
BabyScreen+ newborn screening v0.1514 STRA6 Seb Lunke Classified gene: STRA6 as Red List (low evidence)
BabyScreen+ newborn screening v0.1514 STRA6 Seb Lunke Gene: stra6 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1513 STRA6 Seb Lunke reviewed gene: STRA6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Microphthalmia, syndromic 9, MIM# 601186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1513 STK11 Seb Lunke Marked gene: STK11 as ready
BabyScreen+ newborn screening v0.1513 STK11 Seb Lunke Gene: stk11 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1513 STK11 Seb Lunke Phenotypes for gene: STK11 were changed from Peutz-Jeghers syndrome to Peutz-Jeghers syndrome, MIM# 175200
BabyScreen+ newborn screening v0.1512 STK11 Seb Lunke Publications for gene: STK11 were set to
BabyScreen+ newborn screening v0.1511 STK11 Seb Lunke Classified gene: STK11 as Red List (low evidence)
BabyScreen+ newborn screening v0.1511 STK11 Seb Lunke Gene: stk11 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1510 STK11 Seb Lunke Tag for review tag was added to gene: STK11.
BabyScreen+ newborn screening v0.1510 STK11 Seb Lunke reviewed gene: STK11: Rating: RED; Mode of pathogenicity: None; Publications: 20301443; Phenotypes: Peutz-Jeghers syndrome, MIM# 175200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1510 STAT3 Seb Lunke Marked gene: STAT3 as ready
BabyScreen+ newborn screening v0.1510 STAT3 Seb Lunke Gene: stat3 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1510 STAT3 Seb Lunke Phenotypes for gene: STAT3 were changed from Hyper-IgE recurrent infection syndrome to Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952
BabyScreen+ newborn screening v0.1509 STAT3 Seb Lunke reviewed gene: STAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1509 STAR Seb Lunke Marked gene: STAR as ready
BabyScreen+ newborn screening v0.1509 STAR Seb Lunke Gene: star has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1509 STAR Seb Lunke Phenotypes for gene: STAR were changed from Congenital lipoid adrenal hyperplasia, MIM#201710 to Congenital lipoid adrenal hyperplasia, MIM#201710
BabyScreen+ newborn screening v0.1508 STAR Seb Lunke reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lipoid adrenal hyperplasia (MIM#201710); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1508 STAC3 Seb Lunke Marked gene: STAC3 as ready
BabyScreen+ newborn screening v0.1508 STAC3 Seb Lunke Gene: stac3 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1508 STAC3 Seb Lunke Classified gene: STAC3 as Red List (low evidence)
BabyScreen+ newborn screening v0.1508 STAC3 Seb Lunke Gene: stac3 has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1507 STAC3 Seb Lunke reviewed gene: STAC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, congenital, Baily-Bloch, MIM# 255995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1507 SRP54 Seb Lunke Marked gene: SRP54 as ready
BabyScreen+ newborn screening v0.1507 SRP54 Seb Lunke Gene: srp54 has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1507 SRP54 Seb Lunke reviewed gene: SRP54: Rating: ; Mode of pathogenicity: None; Publications: 20301722; Phenotypes: Neutropaenia, severe congenital, 8, autosomal dominant, MIM# 618752; Mode of inheritance: None
BabyScreen+ newborn screening v0.1507 SRCAP Seb Lunke Marked gene: SRCAP as ready
BabyScreen+ newborn screening v0.1507 SRCAP Seb Lunke Gene: srcap has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1507 SRCAP Seb Lunke Phenotypes for gene: SRCAP were changed from Floating-Harbor syndrome to Floating-Harbor syndrome MIM#136140; Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, MIM# 619595
BabyScreen+ newborn screening v0.1506 SRCAP Seb Lunke Classified gene: SRCAP as Red List (low evidence)
BabyScreen+ newborn screening v0.1506 SRCAP Seb Lunke Gene: srcap has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1505 SRCAP Seb Lunke reviewed gene: SRCAP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Floating-Harbor syndrome MIM#136140, Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, MIM# 619595; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1505 SPTLC1 Seb Lunke Marked gene: SPTLC1 as ready
BabyScreen+ newborn screening v0.1505 SPTLC1 Seb Lunke Gene: sptlc1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1505 SPTLC1 Seb Lunke Phenotypes for gene: SPTLC1 were changed from Neuropathy, hereditary sensory and autonomic, type IA to Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400
BabyScreen+ newborn screening v0.1504 SPTLC1 Seb Lunke Classified gene: SPTLC1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1504 SPTLC1 Seb Lunke Gene: sptlc1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1503 SPTLC1 Seb Lunke reviewed gene: SPTLC1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1503 PRX Zornitza Stark Marked gene: PRX as ready
BabyScreen+ newborn screening v0.1503 PRX Zornitza Stark Gene: prx has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1503 PRX Zornitza Stark Phenotypes for gene: PRX were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, type 4F, MIM# 614895; Dejerine-Sottas disease, MIM# 145900
BabyScreen+ newborn screening v0.1502 PRX Zornitza Stark Classified gene: PRX as Red List (low evidence)
BabyScreen+ newborn screening v0.1502 PRX Zornitza Stark Gene: prx has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1501 PRX Zornitza Stark reviewed gene: PRX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 4F, MIM# 614895, Dejerine-Sottas disease, MIM# 145900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1501 PSAP Zornitza Stark Marked gene: PSAP as ready
BabyScreen+ newborn screening v0.1501 PSAP Zornitza Stark Gene: psap has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1501 PSAP Zornitza Stark Phenotypes for gene: PSAP were changed from Metachromatic leukodystrophy to Parkinson disease; Combined SAP deficiency, MIM# 611721; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Krabbe disease, atypical, MIM# 611722; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900; Gaucher disease, atypical, MIM# 610539
BabyScreen+ newborn screening v0.1500 PSAP Zornitza Stark Mode of inheritance for gene: PSAP was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1499 PSAP Zornitza Stark Classified gene: PSAP as Red List (low evidence)
BabyScreen+ newborn screening v0.1499 PSAP Zornitza Stark Gene: psap has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1498 PSAP Zornitza Stark reviewed gene: PSAP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Parkinson disease, Combined SAP deficiency, MIM# 611721, Encephalopathy due to prosaposin deficiency, MONDO:0012719, Krabbe disease, atypical, MIM# 611722, Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, Gaucher disease, atypical, MIM# 610539; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1498 TMEM67 Lilian Downie reviewed gene: TMEM67: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20232449 PMID: 26092869, PMID: 27336129; Phenotypes: COACH syndrome MIM#216360, Joubert syndrome MIM#10688, Meckel syndrome MIM#607361, Nephronophthisis MIM#613550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1498 TMIE Lilian Downie reviewed gene: TMIE: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301607, PMID: 33987950; Phenotypes: Deafness, autosomal recessive 6 MIM#600971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1498 TMPRSS3 Lilian Downie reviewed gene: TMPRSS3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34868270; Phenotypes: deafness, autosomal recessive MIM#601072; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1498 PTCH1 Zornitza Stark Marked gene: PTCH1 as ready
BabyScreen+ newborn screening v0.1498 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1498 PTCH1 Zornitza Stark Phenotypes for gene: PTCH1 were changed from Nevoid basal cell carcinoma syndrome to Basal cell nevus syndrome, MIM# 109400
BabyScreen+ newborn screening v0.1497 PTCH1 Zornitza Stark Classified gene: PTCH1 as Amber List (moderate evidence)
BabyScreen+ newborn screening v0.1497 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Amber List (Moderate Evidence).
BabyScreen+ newborn screening v0.1496 PTCH1 Zornitza Stark Tag for review tag was added to gene: PTCH1.
Tag cancer tag was added to gene: PTCH1.
BabyScreen+ newborn screening v0.1496 PTCH1 Zornitza Stark reviewed gene: PTCH1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Basal cell nevus syndrome, MIM# 109400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1496 PTEN Zornitza Stark Marked gene: PTEN as ready
BabyScreen+ newborn screening v0.1496 PTEN Zornitza Stark Gene: pten has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1496 PTEN Zornitza Stark Phenotypes for gene: PTEN were changed from Cowden disease; Bannayan-Riley-Ruvalcaba syndrome to Cowden syndrome 1, MIM# 158350; Macrocephaly/autism syndrome, MIM# 605309
BabyScreen+ newborn screening v0.1495 PTEN Zornitza Stark Classified gene: PTEN as Red List (low evidence)
BabyScreen+ newborn screening v0.1495 PTEN Zornitza Stark Gene: pten has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1494 PTEN Zornitza Stark Tag for review tag was added to gene: PTEN.
Tag cancer tag was added to gene: PTEN.
BabyScreen+ newborn screening v0.1494 PTEN Zornitza Stark reviewed gene: PTEN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cowden syndrome 1, MIM# 158350, Macrocephaly/autism syndrome, MIM# 605309; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
BabyScreen+ newborn screening v0.1494 PTF1A Zornitza Stark Marked gene: PTF1A as ready
BabyScreen+ newborn screening v0.1494 PTF1A Zornitza Stark Gene: ptf1a has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1494 PTF1A Zornitza Stark Tag treatable tag was added to gene: PTF1A.
Tag gastrointestinal tag was added to gene: PTF1A.
BabyScreen+ newborn screening v0.1494 PTF1A Zornitza Stark reviewed gene: PTF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pancreatic agenesis 2, MIM# 615935, Pancreatic and cerebellar agenesis, MIM# 609069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1494 PTH1R Zornitza Stark Marked gene: PTH1R as ready
BabyScreen+ newborn screening v0.1494 PTH1R Zornitza Stark Gene: pth1r has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1494 PTH1R Zornitza Stark Phenotypes for gene: PTH1R were changed from Metaphyseal chondrodysplasia to Failure of tooth eruption, primary MIM#125350; Eiken syndrome MIM#600002; Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400; Chondrodysplasia, Blomstrand type MIM#215045
BabyScreen+ newborn screening v0.1493 PTH1R Zornitza Stark Mode of inheritance for gene: PTH1R was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1492 PTH1R Zornitza Stark Classified gene: PTH1R as Red List (low evidence)
BabyScreen+ newborn screening v0.1492 PTH1R Zornitza Stark Gene: pth1r has been classified as Red List (Low Evidence).
BabyScreen+ newborn screening v0.1491 PTH1R Zornitza Stark reviewed gene: PTH1R: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Failure of tooth eruption, primary MIM#125350, Eiken syndrome MIM#600002, Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400, Chondrodysplasia, Blomstrand type MIM#215045; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1491 PTPRC Zornitza Stark Marked gene: PTPRC as ready
BabyScreen+ newborn screening v0.1491 PTPRC Zornitza Stark Gene: ptprc has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1491 PTPRC Zornitza Stark Tag treatable tag was added to gene: PTPRC.
Tag immunological tag was added to gene: PTPRC.
BabyScreen+ newborn screening v0.1491 PTPRC Zornitza Stark reviewed gene: PTPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency, T cell-negative, B-cell/natural killer-cell positive MIM# 608971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
BabyScreen+ newborn screening v0.1491 PYGL Zornitza Stark Marked gene: PYGL as ready
BabyScreen+ newborn screening v0.1491 PYGL Zornitza Stark Gene: pygl has been classified as Green List (High Evidence).
BabyScreen+ newborn screening v0.1491 PYGL Zornitza Stark Phenotypes for gene: PYGL were changed from Glycogen storage disease VI to Glycogen storage disease VI, MIM# 232700
BabyScreen+ newborn screening v0.1490 PYGL Zornitza Stark Tag treatable tag was added to gene: PYGL.
Tag metabolic tag was added to gene: PYGL.
BabyScreen+ newborn screening v0.1490 PYGL Zornitza Stark reviewed gene: PYGL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycogen storage disease VI, MIM# 232700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal