Insights into the pathophysiology of DFNA44 hearing loss associated with CCDC50 frameshift variants.

ABSTRACT: Non-syndromic sensorineural hearing loss (SNHL) is the most common sensory disorder, and it presents a high genetic heterogeneity. As part of our clinical genetic studies, we ascertained a previously unreported mutation in CCDC50 [c.828_858del, p.(Asp276Glufs*40)] segregating with hearing impairment in a Spanish family with SNHL associated with the autosomal dominant deafness locus DFNA44, which is predicted to disrupt protein function. To gain insight into the mechanism behind DFNA44 mutations, we analysed two Ccdc50 presumed loss-of-function mouse mutants, which showed normal hearing thresholds up to 6 months of age, indicating that haploinsufficiency is unlikely to be the pathogenic mechanism. We then carried out in vitro studies on a set of artificial mutants and on the p.(Asp276Glufs*

SUBMITTER: Lachgar-Ruiz M 

PROVIDER: S-EPMC10445743 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature