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| Auditory Neuropathy Spectrum Disorder v1.9 | CABP2 |
Barbara Vona gene: CABP2 was added gene: CABP2 was added to Auditory Neuropathy Spectrum Disorder. Sources: Literature Mode of inheritance for gene: CABP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CABP2 were set to PMID: 28183797 Phenotypes for gene: CABP2 were set to Auditory neuropathy; auditory synaptopathy Penetrance for gene: CABP2 were set to Complete Mode of pathogenicity for gene: CABP2 was set to Other Review for gene: CABP2 was set to RED gene: CABP2 was marked as current diagnostic Added comment: Variants in CABP2 have been reported to cause autosomal recessive non-syndromic hearing loss (DFNB93). In-depth functional studies and deep phenotyping of one of the originally published families with a homozygous loss-of-function variant (NM_016366.3:c.466G>T (p.Glu156Ter)/NM_001318496.2:c.484G>T, p.(Glu162Ter)); PMID: 22981119) presenting mid-frequency, moderate-to-severe hearing loss, uncovered transient evoked otoacoustic emissions (TEOAEs) in a 4 year-old affected individual (PMID: 28183797). The authors suggested, at least initially, that outer hair cell function is spared, thus showing the first individual with auditory synaptopathy/auditory neuropathy. A mouse model with a deletion of exons 3-4 of Cabp2 showed reduced auditory brainstem response recordings and present distortion product otoacoustic emissions. The lesion was identified to be most likely at the inner hair cell synapses, compatible with an auditory synaptopathy/auditory neuropathy. Although there are not abundant examples of CABP2 patients with auditory synapthpathy/auditory neuropathy in the literature, biallelic variants in CABP2 undoubtedly cause hearing impairment that should be further phenotyped in patients through OAE testing. Replication of this specific type of hearing deficit is needed; therefore, CABP2 merits being added to the Auditory Neuropathy gene panel. Sources: Literature |
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| 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 |
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| Auditory Neuropathy Spectrum Disorder v1.9 | TMEM43 |
Barbara Vona gene: TMEM43 was added gene: TMEM43 was added to Auditory Neuropathy Spectrum Disorder. Sources: Literature Mode of inheritance for gene: TMEM43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TMEM43 were set to PMID: 34050020 Phenotypes for gene: TMEM43 were set to Auditory neuropathy Penetrance for gene: TMEM43 were set to Complete Review for gene: TMEM43 was set to RED Added comment: Two families with autosomal dominant inheritance patterns segregated the same p.(Arg372Ter) variant in TMEM43. Affected individuals reported late onset and progressive auditory neuropathy and were able to hear sound but not discriminate speech. Following cochlear implantation, speech discrimination was fully restored. A knock-in mouse was studied that recapitulated the progressive hearing impairment that was observed in the affected individuals. This gene has been assigned to the AUNA3 locus (OMIM: #619832). Sources: Literature |
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| Auditory Neuropathy Spectrum Disorder v1.9 | OPA1 | Arina Puzriakova Phenotypes for gene: OPA1 were changed from 125250 to Optic atrophy 1, OMIM:165500; Optic atrophy plus syndrome, OMIM:125250 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Auditory Neuropathy Spectrum Disorder v1.8 | DIAPH3 | Eleanor Williams Publications for gene: DIAPH3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Auditory Neuropathy Spectrum Disorder v1.7 | DIAPH3 | Eleanor Williams Mode of inheritance for gene: DIAPH3 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Auditory Neuropathy Spectrum Disorder v1.6 | DIAPH3 | Eleanor Williams Classified gene: DIAPH3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Auditory Neuropathy Spectrum Disorder v1.6 | DIAPH3 | Eleanor Williams Added comment: Comment on list classification: 2 cases reported so changing rating from red to amber | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Auditory Neuropathy Spectrum Disorder v1.6 | DIAPH3 | Eleanor Williams Gene: diaph3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Auditory Neuropathy Spectrum Disorder v1.5 | DIAPH3 | Eleanor Williams commented on gene: DIAPH3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Auditory Neuropathy Spectrum Disorder | DFNB59 | Louise Daugherty commented on DFNB59 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||