Deafness_Isolated

Gene: ATP11A

Green List (high evidence)

PMID 35278131 reports three additional families, including segregation in a large pedigree.

Created: 26 May 2023, 12:29 a.m. | Last Modified: 26 May 2023, 12:29 a.m.

Panel Version: 1.43

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Deafness, autosomal dominant 84, MIM# 619810; Auditory neuropathy, autosomal dominant 2, MIM# 620384

Publications

• 35278131

I don't know

PMID: 36300302:
- A family with non-syndromic autosomal-dominant auditory neuropathy/auditory synaptopathy. The same family previously published in PMID: 28601886 Lang-Rogh 2017.
- 5500 bp deletion involving the last coding exon of both RefSeq annotated ATP11A isoforms.
- Present in 10 affected individuals from a multi-generational family, absent in 2 unaffected family members tested.
- RNA studies showed ATP11A deletion allele did not undergo NMD, and led to an inclusion of a pseudoexon of 117 bp size, resulting in a novel 38 amino-acid spanning C-terminus of the mutant protein.
- Mutant ATP11A had normal subcellular localisation.
- Studies in mice showed ATP11A protein is expressed in mouse inner ear, conditional Atp11a ko mice showed age-progressive dysfunction or loss of spiral ganglion neurons.

Created: 3 Nov 2022, 3:56 a.m. | Last Modified: 3 Nov 2022, 3:56 a.m.

Panel Version: 1.37

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Deafness, autosomal dominant 84 (MIM#619810)

Publications

• PMID: 36300302

Variants in this GENE are reported as part of current diagnostic practice

I don't know

Three families described with autosomal dominant non-syndromic deafness:

A Canadian family of European ancestry was described with a novel variant affecting splicing of the 3'UTR of one isoform of ATP11A. RNA studies showed the retention of 153bp of intronic sequence in the 3'UTR. Other isoforms may be variably affected. The variant is deep intronic in the two RefSeq transcripts. Variant was present in 17 affected and absent in 19 unaffected individuals.

Two Jewish Israeli families, one originating from Uzbekistan and one from Afghanistan, described with the same splice variant. RNA studies confirmed extension of the penultimate exon and a PTC (not NMD predicted). Variant segregated in 8 affected individuals, absent from 3 tested unaffected individuals.
Sources: Literature

Created: 7 Apr 2022, 1:29 a.m. | Last Modified: 7 Apr 2022, 1:37 a.m.

Panel Version: 1.25

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

Phenotypes
Deafness, autosomal dominant 84 MIM#619810

Publications

• 35278131

Variants in this GENE are reported as part of current diagnostic practice