Here, we report that the Cx30-A88V mutant, despite being toxic to inner ear-derived HEI-OC1 cells, conferred remarkable long-term protection against age-related high frequency hearing loss in Cx30<sup>A88V/A88V</sup> mice.
Targeted exome sequencing further identified the causal mutations in the remaining seven families: CIB2:c.97C > T; p.(Arg33*), MYO7A:c.470+1G > A; p.(?), and SLC26A4:c.410C > T; p.(Ser137Leu) biallelic mutations in two families each, and a TECTA:c.2743 A > G; p.(Ile915Val) monoallelic mutation in the only family with autosomal dominant transmission of the HI.
The other case presented is that of a family with Clouston syndrome (caused by p.Gly11Arg mutation in GJB6), who are the first reported patients of Polish origin suffering from this disorder.
Our findings provide further evidence of a correlation between the p.R75Q mutation in Cx26 and a syndromic hearing impairment with palmoplantar keratoderma.
Our findings provide further evidence of a correlation between the p.R75Q mutation in Cx26 and a syndromic hearing impairment with palmoplantar keratoderma.
A total of 81.37% of patients harboured at least one c.35delG allele; c.167delT and c.-23 + 1G> A were identified in 10.78% and the 9.8% of patients respectively; c.35delG homozygotes presented more severe hearing impairment (75.59% of profound hearing loss) and a higher mean PTA0.25-4 kHz (96.79 ± 21.11 dB HL) with respect to c.35delG/non-c.35delG and c.35delG/Wt patients (P < 0.05).
The loss-of-function V37E mutant associated with Clouston syndrome or keratitis-ichthyosis-deafness syndrome was retained in the endoplasmic reticulum and significantly induced apoptosis.
Lastly, the A88V mutant, which is linked to the development of Clouston syndrome, also significantly induced apoptosis but through an endoplasmic-reticulum-independent mechanism.
Lastly, the A88V mutant, which is linked to the development of Clouston syndrome, also significantly induced apoptosis but through an endoplasmic-reticulum-independent mechanism.