Rebecca Foulger Added comment: Comment on mode of inheritance: Kept Mode of Inheritance as 'BOTH monoallelic and biallelic' based on post-Webex review from Helen Lord.
Rebecca Foulger Mode of inheritance for gene: CACNA1D was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rebecca Foulger commented on gene: CACNA1D: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
Helen Lord reviewed gene: CACNA1D: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rebecca Foulger edited their review of gene: CACNA1D: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green. ; Changed rating: AMBER
Tracy Lester reviewed gene: CACNA1D: 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: 23913001 , 28472301 ; Phenotypes: Primary aldosteronism, seizures, and neurologic abnormalities,615474, Sinoatrial node dysfunction and deafness,614896; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rebecca Foulger Added comment: Comment on mode of inheritance: Primary aldosteronism, seizures, and neurologic abnormalities (MIM: 615474) has AD inheritance. Seizures are not generally reported for the biallelic disorder Sinoatrial node dysfunction and deafness (MIM:614896). However, PMID:30054272 report an Arabic individual from consanguineous parents with moderate hearing impairment, ID, DD and epilepsy and a homozygous missense variant in CACNA1D (Gln567His). Seizures began age 4 months. The individual also had a homozygous OTOG variant, but this was present in a heterozygous state in the gnomAD browser. Both parents were heterozygous for the OTOG and CACNA1D variants.
Rebecca Foulger Mode of inheritance for gene: CACNA1D was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal