Abstract
BACKGROUND: Hearing loss is an economically and socially important cause of human morbidity, affecting 360 million people (over 5% of the world's population), of whom 32 million are children. Of the estimated minimum of 50% of hereditary hearing loss, non-syndromic hearing loss (NSHL) accounts for more than 70%. The autosomal dominant non-syndromic hearing loss (ADNSHL) is highly heterogeneous. To date, 67 ADNSHL loci (DFNA1-67) have been mapped; however, only 35 causative genes have been cloned since 1997 (http://hereditaryhearingloss.org/). METHODS: To identify the genetic basis of hereditary hearing loss in a Chinese family with ADNSHL, we undertook a targeted sequencing of 180 genes using a custom capture panel (MiamiOtoGenes). RESULTS: The onset of hearing loss in the family occurred between the ages of 15 and 18 years. Hearing loss was bilateral, started in the high frequency and progressed to lower frequencies. The c.353A>T (K118M) in the AC TG1 gene was identified by panel and was confirmed by Sanger sequencing and was present in all affected family members. So far, five of the 23 DFNA20/26 families worldwide have been found to carry mutation involving the residue K118. CONCLUSIONS: This is the first report of K118M mutation in the ACTG1 gene causing hearing loss in the Chinese population. The present data are in line with previous evidence to suggest that codon K118 of ACTG1 may represent a mutational hot spot that justifies a mutation screen for diagnostic purpose in the genetically heterogeneous group of DFNA20/26.