Abstract
Background
Hearing loss is the most common sensory nervous system defect in humans. Approximately half of hearing loss cases have a genetic etiology. At present, more than 300 genes and 1000 mutations have been identified that cause hereditary hearing loss (HHL). However, there are still a large number of unknown genes related to hearing loss.
Objective
The purpose of this study was to analyze the clinical audiological characteristics of a family with hereditary nonsyndromic hearing loss (NSHL) and identify the mutation of deafness‐related genes.
Material and Methods
A Chinese Han–dominant deafness family including six members was enrolled in our study. In addition to collecting detailed clinical data on the audiology of this family, we employed whole‐exome sequencing (WES) and Sanger sequencing to identify the key gene causing deafness.
Results
The pedigree chart of the HHL family suggested that the disease might be a dominant genetic disease. The WES and Sanger sequencing indicated that a novel mutation (c.842C > G) occurred in the ACTG1 gene on the fifth exon, which caused the change of the coding protein (p.S281C). This variant cosegregated perfectly with the hearing loss phenotype: All affected members carried the heterozygous c.842C > G mutation, whereas the only unaffected family member showed wild‐type ACTG1. Multiple sequence alignment revealed that the p.Ser281 residue was highly conserved across vertebrate species. Bioinformatic analyses showed high conservation of p.Ser281 across species and predicted damaging effects on protein structure and function.
Conclusions and Significance
On the basis of our research, we identified a novel pathogenic variant in the ACTG1 gene responsible for NSHL, which expands the mutational spectrum of ACTG1‐related hearing loss. Further in vitro and in vivo studies may be performed to elucidate the underlying mechanism by which ACTG1 contributes to hearing function, potentially providing intervention targets for gene therapy of HHL.