Ataxia and cerebellar anomalies - narrow panel

Gene: ATP6V0C

I don't know

Comment on list classification: There are 9 unrelated families reported in literature with individuals habouring CNVs at 16p13.3, with early-onset progressive ataxia and cognitive decline. ATP6V0C is the most likely candidate gene, as it was the only one present in the minimal region of overlap for all patients. However, these structural variants would not be detected in the current NGS analysis pipeline and this gene should remain Amber.

Created: 29 Dec 2025, 3:25 p.m. | Last Modified: 29 Dec 2025, 3:38 p.m.

Panel Version: 8.39

PMID: 41349538 Fasham et al., 2025
Report of 11 individuals from 9 unrelated families with copy-number gains at 16p13.3, with early-onset progressive ataxia and cognitive decline (9-32 years). Method: mostly microarray + WGS. The structural variants arose de novo in 5 patients, one was inherited from an unaffected mosaic father, and 2 inherited from an affected mother; 3 cases with unknown inheritance. In addition to cognitive impairment and progressive ataxia, individuals presented with: regression 8/10, dysarthria 10/11, axonal neuropathy 9/11, nystagmus 4/11, pes cavus 5/6, scoliosis/kyphosis 7/10, optic atrophy 2/10.
Cerebellar and caudate atrophy was seen in 11/11 individuals.

The minimal region of overlap for all patients included a single gene (ATP6V0C); RNA-seq using whole-blood and fibroblast/lymphoblast cultures indicated increased expression of several genes within the SV, with ATP6V0C showing the most significant increase. Hence, ATP6V0C is the mostly likely candidate gene.

ATP6V0C is linked to Epilepsy, early-onset, 3, with or without developmental delay, MIM:620465 in OMIM (accessed 29th Dec 2025).
Sources: Literature

Created: 29 Dec 2025, 1:59 p.m. | Last Modified: 29 Dec 2025, 2:01 p.m.

Panel Version: 8.37

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
progressive ataxia and cognitive decline

Publications

• 41349538