Early onset or syndromic epilepsy

Gene: ATP6V0C

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 1:13 p.m. | Last Modified: 6 May 2024, 9:17 p.m.

Panel Version: 5.6

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.

Created: 24 Aug 2023, 8:33 a.m. | Last Modified: 24 Aug 2023, 8:33 a.m.

Panel Version: 4.92

PMID:36074901 - 21 of 27 patients identified with monoallelic ATP6V0C variants, including a patient each from PMID:24623842 and PMID:33190975 had seizures with age of onset ranging from five months to 12 years. In addition, knockdown of the orthologous Atp6v0c gene in Drosophila resulted in seizure-like behavior.

PMID:35600075 - Six individuals from two unrelated Chinese families presented with early-onset epilepsy manifesting as self-limited febrile seizures or generalised epilepsy with febrile seizures-plus and they harboured heterozygous ATP6V0C variants.

PMID:37161035 - All three unrelated patients identified with monoallelic ATP6V0C variants had seizures, while two had impaired intellectual development or developmental delay.

This gene has been associated with relevant phenotypes in OMIM (MIM #620465) and Gene2Phenotype (with 'strong' rating in the DD panel).

Created: 24 Aug 2023, 8:13 a.m. | Last Modified: 24 Aug 2023, 8:13 a.m.

Panel Version: 4.87

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465

Publications

• 24623842
• 33190975
• 35600075
• 36074901
• 37161035

Green List (high evidence)

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, 2:16 p.m. | Last Modified: 21 Aug 2023, 2:16 p.m.

Panel Version: 4.85

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy; Intellectual Disability; Microcephaly

Publications

• 36074901

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

I don't know

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: Literature

Created: 11 Oct 2021, 7:26 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy; Intellectual Disability; microcephaly

Publications

• 33190975
• 33090716