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Prepair 1000+ v1.1285 HACE1 Zornitza Stark Marked gene: HACE1 as ready
Prepair 1000+ v1.1285 HACE1 Zornitza Stark Gene: hace1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1285 HACE1 Zornitza Stark Phenotypes for gene: HACE1 were changed from Spastic paraplegia and psychomotor retardation with or without seizures, 616756 (3), Autosomal recessive to Spastic paraplegia and psychomotor retardation with or without seizures, MIM#616756
Prepair 1000+ v1.1284 HACE1 Zornitza Stark Publications for gene: HACE1 were set to
Prepair 1000+ v1.1257 HACE1 Clare Hunt reviewed gene: HACE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26437029, 26424145, 31321300; Phenotypes: Spastic paraplegia and psychomotor retardation with or without seizures, 616756, MONDO:0014764; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1145 NAA10 Zornitza Stark Phenotypes for gene: NAA10 were changed from N-terminal acetyltransferase deficiency, 300855 (3) to Ogden syndrome (MIM#300855); Syndromic microphthalmia 1 (MIM#309800)
Prepair 1000+ v1.1002 NAGS Zornitza Stark Phenotypes for gene: NAGS were changed from N-acetylglutamate synthase deficiency, 237310 (3) to N-acetylglutamate synthase deficiency MIM#237310
Prepair 1000+ v1.992 NAGS Michelle Torres reviewed gene: NAGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 12594532, 17421020, 12459178, 12754705, 9877039; Phenotypes: N-acetylglutamate synthase deficiency MIM#237310; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.992 POR Ee Ming Wong changed review comment from: - PORD (P450 oxidoreductase deficiency) is associated with disorders of sex development in both sexes, where Antley-Bixler (ABS) syndrome is the name given to the severe form
- Skeletal abnormalities of the ABS phenotype are frequently observed in individuals with PORD, characterised by craniosynostosis, brachycephaly, radio-ulnar or radio-humeral synostosis, bowed femora, arachnodactyly, midface hypoplasia, proptosis, and choanal stenosis. The severity of malformations varies from mild to moderate and severe.

NB: Only the more severe MIM# has been added to this gene list.; to: - PORD (P450 oxidoreductase deficiency) is associated with disorders of sex development in both sexes, where Antley-Bixler (ABS) syndrome is the name given to the severe form
- Skeletal abnormalities of the ABS phenotype are frequently observed in individuals with PORD, characterised by craniosynostosis, brachycephaly, radio-ulnar or radio-humeral synostosis, bowed femora, arachnodactyly, midface hypoplasia, proptosis, and choanal stenosis. The severity of malformations varies from mild to moderate and severe.
- Congenital onset

NB: Only the more severe MIM# has been added to this gene list.
Prepair 1000+ v1.961 CHRNE Lilian Downie Phenotypes for gene: CHRNE were changed from Myasthenic syndrome, congenital, 4A, slow-channel, 605809 (3) to Myasthenic syndrome, congenital, 4A, slow-channel MIM#605809; Myasthenic syndrome, congenital, 4B, fast-channel MIM#616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency MIM#608931
Prepair 1000+ v1.941 CHRNE Lilian Downie reviewed gene: CHRNE: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301347; Phenotypes: Myasthenic syndrome, congenital, 4A, slow-channel MIM#605809, Myasthenic syndrome, congenital, 4B, fast-channel MIM#616324, Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency MIM#608931; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.761 TPRKB Lucy Spencer changed review comment from: Gene is red on Mackenzie's mission panel but the review itself is green and says "Three unrelated families reported with renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly." this is refering to 3 families all with homozygous missense, p.Lys65Met, p.Tyr149Cys, and p.Leu136Pro.

There has been at least one more individual reported PMID: 38628357: a three-year-old male with developmental delay, regression, microcephaly, distinctive facial features, skeletal abnormalities, and epilepsy. He also had relapsing nephrotic proteinuria exacerbated by upper respiratory tract infections and progressive renal function decline. He was compound heterozygous for p.(Ser76IlefsTer3) and c.247C>T, p.(Leu83Phe).

Severe early-onset and reported in at least 4 individuals (also green on mendeliome), upgrading to green here.; to: Gene is red on Mackenzie's mission panel but the review itself is green and says "Three unrelated families reported with renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly." this is refering to 3 families all with homozygous missense, p.Lys65Met, p.Tyr149Cys, and p.Leu136Pro (PMIDs: 28805828, 30053862).

There has been at least one more individual reported PMID: 38628357: a three-year-old male with developmental delay, regression, microcephaly, distinctive facial features, skeletal abnormalities, and epilepsy. He also had relapsing nephrotic proteinuria exacerbated by upper respiratory tract infections and progressive renal function decline. He was compound heterozygous for p.(Ser76IlefsTer3) and c.247C>T, p.(Leu83Phe).

Severe early-onset and reported in at least 4 individuals (also green on mendeliome), upgrading to green here.
Prepair 1000+ v1.559 ACAT1 Zornitza Stark Phenotypes for gene: ACAT1 were changed from Alpha-methylacetoacetic aciduria, 203750 (3) to Alpha-methylacetoacetic aciduria, MIM#203750
Prepair 1000+ v1.557 ACAT1 Zornitza Stark reviewed gene: ACAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17236799, 1715688; Phenotypes: Alpha-methylacetoacetic aciduria, MIM#203750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.556 ACE Lilian Downie Marked gene: ACE as ready
Prepair 1000+ v1.556 ACE Lilian Downie Gene: ace has been classified as Green List (High Evidence).
Prepair 1000+ v1.556 ACE Lilian Downie Publications for gene: ACE were set to
Prepair 1000+ v1.547 ACE Lauren Rogers reviewed gene: ACE: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116425, 22095942; Phenotypes: Renal tubular dysgenesis, MIM# 267430; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.546 IFNGR1 Andrew Coventry changed review comment from: Multiple families with recessive disease reported, reviewed in PMID 15589309.
Patients with complete IFNGR1 deficiency have a severe clinical phenotype characterized by early and often fatal mycobacterial infections. The disorder can thus be categorized as a form of mendelian susceptibility to mycobacterial disease (MSMD). Bacillus Calmette-Guerin (BCG) and environmental mycobacteria are the most frequent pathogens, and infection typically begins before the age of 3 years. Recessive deficiency is thought to result in complete loss of cellular response to IFNG and absence of surface IFNGR1 expression. Animal models present.

Note: AD condition associated with this gene - Immunodeficiency 27B, mycobacteriosis, MIM#615978.
Dominant deficiency is typically due to cytoplasmic domain truncations resulting in accumulation of non-functional IFNGR1 proteins that may impede the function of molecules encoded by the wildtype allele, thereby leading to diminished but not absent responsiveness to IFNG. Common deletions at and around nucleotide 818. (PMID: 10192386); to: Multiple families with recessive disease reported, reviewed in PMID 15589309.
Patients with complete IFNGR1 deficiency have a severe clinical phenotype characterized by early and often fatal mycobacterial infections. The disorder can thus be categorized as a form of mendelian susceptibility to mycobacterial disease (MSMD). Bacillus Calmette-Guerin (BCG) and environmental mycobacteria are the most frequent pathogens, and infection typically begins before the age of 3 years. Recessive deficiency is thought to result in complete loss of cellular response to IFNG and absence of surface IFNGR1 expression. Animal models present.

Note: AD condition associated with this gene - Immunodeficiency 27B, mycobacteriosis, MIM#615978.
Dominant deficiency is typically due to cytoplasmic domain truncations resulting in accumulation of non-functional IFNGR1 proteins that may impede the function of molecules encoded by the wildtype allele, thereby leading to diminished but not absent responsiveness to IFNG. Deletions including nucleotide 818 reported. (PMID: 10192386)
Prepair 1000+ v1.519 RAPSN Zornitza Stark Phenotypes for gene: RAPSN were changed from Fetal akinesia deformation sequence, 208150 (3) to Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency MIM#616326; Fetal akinesia deformation sequence 2 MIM#618388
Prepair 1000+ v1.486 RAPSN Lucy Spencer reviewed gene: RAPSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 17594401; Phenotypes: Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency MIM#616326, Fetal akinesia deformation sequence 2 MIM#618388; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 KCTD7 Lucy Spencer reviewed gene: KCTD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 3, with or without intracellular inclusions MIM#611726; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.187 COLQ Marta Cifuentes Ochoa changed review comment from: Patients with congenital myasthenic syndromes present clinically with onset of variable muscle weakness between infancy and adulthood.

Well established gene-disease association, more than 10 families reported.
HGNC approved symbol/name: COLQ
Is the phenotype(s) severe and onset <18yo ? Y
Known technical challenges?N; to: Patients with congenital myasthenic syndromes present clinically with onset of variable muscle weakness between infancy and adulthood.
Presentations:
-neonatal: respiratory insufficiency, multiple joint contractures (often described as arthrogryposis multiplex congenita) resulting from a lack of fetal movement in utero. Feeding difficulties, poor suck and cry, choking spells, eyelid ptosis, and facial, bulbar, and generalized weakness.In some individuals, long face, narrow jaw, and a high-arched palate have been reported
-childhood: delayed motr milestones, fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness. Ptosis may involve one or both eyelids. Facial and bulbar weakness with nasal speech and difficulties in coughing and swallowing may be present.Spinal deformity or muscle atrophy may occur
-limb-girdle

Well established gene-disease association, more than 10 families reported.
HGNC approved symbol/name: COLQ
Is the phenotype(s) severe and onset <18yo ? Y
Known technical challenges?N
Prepair 1000+ v1.4 PIEZO1 Crystle Lee gene: PIEZO1 was added
gene: PIEZO1 was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: PIEZO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIEZO1 were set to PMID: 26333996
Phenotypes for gene: PIEZO1 were set to Lymphatic malformation 6, MIM#616843
Review for gene: PIEZO1 was set to GREEN
Added comment: Biallelic mutations in PIEZO1 reported in 10 patients from 6 families with generalized lymphatic dysplasia (GLD) This is characterized by a uniform, widespread lymphedema affecting all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions.
Sources: Literature
Prepair 1000+ v1.3 NAGS Seb Lunke Added phenotypes N-acetylglutamate synthase deficiency, 237310 (3) for gene: NAGS
Prepair 1000+ v1.3 MUSK Seb Lunke Added phenotypes Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, 616325 (3) for gene: MUSK
Prepair 1000+ v1.3 ACAT1 Seb Lunke Added phenotypes Alpha-methylacetoacetic aciduria, 203750 (3) for gene: ACAT1
Prepair 1000+ v0.181 IGHM Zornitza Stark changed review comment from: Workaround in place to detect variants in this gene.; to: Workaround possible to detect variants in this gene. However, residual risk of false negative results.
Prepair 1000+ v0.85 PYGM Crystle Lee gene: PYGM was added
gene: PYGM was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: PYGM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PYGM were set to McArdle disease (MIM#232600)
Review for gene: PYGM was set to AMBER
Added comment: Gene-disease association for bi-allelic variants is well established.

McCardle disease: glycogen storage disease type V (GSD5), characterized by onset of exercise intolerance and muscle cramps in childhood or adolescence. Transient myoglobinuria may occur after exercise, due to rhabdomyolysis. Severe myoglobinuria may lead to acute renal failure. Patients may report muscle weakness, myalgia, and lack of endurance since childhood or adolescence. Later in adult life, there is persistent and progressive muscle weakness and atrophy with fatty replacement. McArdle disease is a relatively benign disorder, except for possible renal failure as a complication of myoglobinuria

Clinical heterogeneity exists; about 10% of all affected individuals have mild manifestations (e.g., fatigue or poor stamina without contractures) and remain virtually asymptomatic during daily activities of living(Gene Reviews)
Sources: Literature
Prepair 1000+ v0.0 NAGS Zornitza Stark gene: NAGS was added
gene: NAGS was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NAGS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NAGS were set to N-acetylglutamate synthase deficiency, 237310 (3)
Prepair 1000+ v0.0 NAA10 Zornitza Stark gene: NAA10 was added
gene: NAA10 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: NAA10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: NAA10 were set to N-terminal acetyltransferase deficiency, 300855 (3)
Prepair 1000+ v0.0 MUSK Zornitza Stark gene: MUSK was added
gene: MUSK was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: MUSK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MUSK were set to Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, 616325 (3)
Prepair 1000+ v0.0 KCTD7 Zornitza Stark gene: KCTD7 was added
gene: KCTD7 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: KCTD7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KCTD7 were set to Epilepsy, progressive myoclonic 3, with or without intracellular inclusions, 611726 (3)
Prepair 1000+ v0.0 HACE1 Zornitza Stark gene: HACE1 was added
gene: HACE1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: HACE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HACE1 were set to Spastic paraplegia and psychomotor retardation with or without seizures, 616756 (3), Autosomal recessive
Prepair 1000+ v0.0 ACE Zornitza Stark gene: ACE was added
gene: ACE was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ACE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ACE were set to Renal tubular dysgenesis, 267430 (3)
Prepair 1000+ v0.0 ACAT1 Zornitza Stark gene: ACAT1 was added
gene: ACAT1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ACAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ACAT1 were set to Alpha-methylacetoacetic aciduria, 203750 (3)