Monogenic hearing loss

Gene: ATP11A

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 5 Dec 2024, 8:33 p.m. | Last Modified: 5 Dec 2024, 8:33 p.m.

Panel Version: 4.62

Comment on list classification: This gene should be rated GREEN as it has been implicated in sensorineural hearing loss from four unrelated families, and supported by functional studies from mouse model.

Created: 23 Mar 2023, 4:42 p.m. | Last Modified: 23 Mar 2023, 4:42 p.m.

Panel Version: 4.3

A heterozygous cryptic donor splice site variant in ATP11A has been identified in a large 6-generation family from Newfoundland in which 16 individuals had progressive sensorineural hearing loss. In addition, several individuals with postlingual-onset progressive hearing loss from two unrelated multigenerational Jewish Israeli families with their origins in Uzbekistan and Afghanistan were also identified with a novel duplication in ATP11A (PMID:35278131).

5500 bp deletion involving the last coding exon of both ATP11A isoforms were identified in the large German multi-generational family that was first reported in PMID:28601886 with auditory synaptopathy/neuropathy, which is a distinct type of sensorineural hearing loss. The deletion is present in all affected individuals from the family and absent in two unaffected family members tested (PMID:36300302).

Functional studies in mice showed ATP11A protein is expressed in mouse inner ear and conditional Atp11a knockout mice showed age-progressive dysfunction or loss of spiral ganglion neurons, recapitulating the human phenotype of auditory neuropathy (PMID:36300302).

This gene has been associated with relevant phenotypes in OMIM, but not in Gene2Phenotype.
Sources: Literature

Created: 23 Mar 2023, 4:41 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Deafness, autosomal dominant 84, OMIM:619810

Publications

• 35278131
• 36300302