Severe microcephaly
Gene: ATP6V0C
Comment on list classification: There is sufficient evidence available for promoting this gene to green rating in the next GMS review.Created: 30 Aug 2023, 9:33 a.m. | Last Modified: 30 Aug 2023, 9:33 a.m.
Panel Version: 4.31
PMID:36074901 - 5 out of 27 patients had severe microcephaly (having occipitofrontal circumference (OFC) beyond 3 SD below the mean for their age).
This gene has been associated with relevant phenotypes in both OMIM (MIM #620465) and Gene2Phenotype (with 'strong' rating in the DD panel). OMIM has recorded microcephaly as a clinical presentation manifesting only in some patients with autosomal dominant ATP6V0C variants.Created: 30 Aug 2023, 9:30 a.m. | Last Modified: 30 Aug 2023, 9:30 a.m.
Panel Version: 4.28
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Publications
Twenty seven patients reported in 2023 by Mattison et al (including those from the earlier papers in 2014 and 2021). De novo heterozygous missense, frameshift, and one stop-loss variant reported. Haploinsufficiency reported as the most likely mechanism, but a dominant-negative effect is also postulated. At least four cases of mosaicism detected.
Highly variable condition with epilepsy and/or intellectual disability as the main features. Microcephaly and non-specific dysmorphic features in some cases. Incomplete penetrance in some families.Created: 21 Aug 2023, 2:19 p.m. | Last Modified: 21 Aug 2023, 2:19 p.m.
Panel Version: 4.28
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Epilepsy; Intellectual Disability; Microcephaly
Publications
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.Created: 13 Oct 2021, 12:39 p.m. | Last Modified: 13 Oct 2021, 12:39 p.m.
Panel Version: 3.1354
9 individuals reported with deletions and ID/seizures/microcephaly, minimum overlapping region implicates ATP6V0C as the causative gene. Single case report of de novo SNV and ID/seizures.
Sources: LiteratureCreated: 11 Oct 2021, 7:26 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Epilepsy; Intellectual Disability; microcephaly
Publications
Tag watchlist was removed from gene: ATP6V0C. Tag Q3_23_promote_green tag was added to gene: ATP6V0C. Tag Q3_23_NHS_review tag was added to gene: ATP6V0C.
Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: ATP6V0C were changed from Epilepsy; Intellectual Disability; microcephaly to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Publications for gene: ATP6V0C were set to 33190975; 33090716
gene: ATP6V0C was added gene: ATP6V0C was added to Severe microcephaly. Sources: Literature,Expert Review Amber watchlist tags were added to gene: ATP6V0C. Mode of inheritance for gene: ATP6V0C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP6V0C were set to 33190975; 33090716 Phenotypes for gene: ATP6V0C were set to Epilepsy; Intellectual Disability; microcephaly