| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Auditory Neuropathy Spectrum Disorder v1.9 | ATP11A |
Barbara Vona gene: ATP11A was added gene: ATP11A was added to Auditory Neuropathy Spectrum Disorder. Sources: Literature Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP11A were set to PMID: 36300302; 28601886 Phenotypes for gene: ATP11A were set to Auditory synaptopathy/neuropathy; AUNA2 Penetrance for gene: ATP11A were set to Complete Mode of pathogenicity for gene: ATP11A was set to Other Review for gene: ATP11A was set to RED gene: ATP11A was marked as current diagnostic Added comment: A large German family with auditory synaptopathy/neuropathy that originally mapped the AUNA2 locus to either chromosome 12q24 or 13q34 underwent genome sequencing. Affected individuals showed symmetrical, slowly progressive postlingual hearing loss starting late in the first decade that eventually advanced to to severe hearing impairment in the fifth decade. Auditory brainstem response thresholds were worse than otoacoustic emissions, suggesting a deficit in neural sound encoding. A 5.5 kb deletion encompassing the last coding exon of both RefSeq annotated ATP11A isoforms was found to segregate with the phenotype. RNA studies from an affected individual confirmed stable expression and both a deletion and activation of a cryptic splice acceptor that leads to inclusion of a pseudoexon and novel 38 amino acids at the C-terminus. ATP11A flippase activity was disrupted in mutant cells, compatible with a loss-of-function mechanism, although a gain of function of dominant negative effect could not be excluded. ATP11A is expressed in the mouse inner ear. Its function was explored in depth using a conditional knockout mouse that showed a progressive dysfunction or loss of spiral ganglion neurons. Additional families are needed to replicate an auditory synaptopathy/neuropathy phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||