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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+ v1.648 IDS Zornitza Stark Marked gene: IDS as ready
Prepair 1000+ v1.648 IDS Zornitza Stark Gene: ids has been classified as Green List (High Evidence).
Prepair 1000+ v1.648 IDS Zornitza Stark Phenotypes for gene: IDS were changed from Mucopolysaccharidosis II, 309900 (3) to Mucopolysaccharidosis II, MIM# 309900; Hunter syndrome, MONDO:0010674
Prepair 1000+ v1.647 IDS Zornitza Stark Publications for gene: IDS were set to
Prepair 1000+ v1.633 IDS Ee Ming Wong reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301451; Phenotypes: Mucopolysaccharidosis II, MIM# 309900, Hunter syndrome, MONDO:0010674; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Prepair 1000+ v1.384 TSPYL1 Lilian Downie Added comment: Comment when marking as ready: Originally reported only in Amish community, founder variant
subsequently reported in 3 unrelated families, non amish - GREEN AT UPGRADE
2 cohort studies looking for variants in this gene in SIDS cohorts but it's very rare and presents with more of a progressive neurological phenotype in the non Amish families
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+ v1.143 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID:38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Prepair 1000+ v1.65 CLCNKB Lucy Spencer changed review comment from: Is the phenotype(s) severe and onset <18yo? YES. CLCNKB mutations cause Bartter syndrome type 3 also called classic Bartter syndrome with renal salt wasting, hypokalemia, metabolic alkalosis, polyuria, polydipsia, and failure to thrive. It typically manifests in early childhood but late childhood or adulthood onset cases have been reported. Classic Bartter syndrome has a heterogeneous presentation from severe to very mild (PMIDs: 25810436, 24965226)

There is also a digenic inheritance known for this gene with variants in CLCNKA causing Bartter syndrome type 4b.; to: Is the phenotype(s) severe and onset <18yo? YES. CLCNKB mutations cause Bartter syndrome type 3 also called classic Bartter syndrome with renal salt wasting, hypokalemia, metabolic alkalosis, polyuria, polydipsia, and failure to thrive. It typically manifests in early childhood but late childhood or adulthood onset cases have been reported. Classic Bartter syndrome has a heterogeneous presentation from severe to very mild (PMIDs: 25810436, 24965226)

There is also a digenic inheritance known for this gene with variants in CLCNKA causing Bartter syndrome type 4b.
Prepair 1000+ v1.3 IDS Seb Lunke Added phenotypes Mucopolysaccharidosis II, 309900 (3) for gene: IDS
Prepair 1000+ v0.0 IDS Zornitza Stark gene: IDS was added
gene: IDS was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: IDS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: IDS were set to Mucopolysaccharidosis II, 309900 (3)