Identification of as a Significant Contributor to Autosomal Recessive Hearing Loss in the Chinese Population.

Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Mutations in the (transmembrane protease, serine 3) gene cause prelingual (DFNB10) or postlingual (DFNB8) deafness. In our previous study, three pathogenic mutations in were identified in one Chinese family. To evaluate the importance of mutations in recessive deafness among the Chinese, we screened 150 autosomal recessive nonsyndromic hearing loss (ARNSHL) families and identified 6 that carried seven causative mutations, including five novel mutations (c.809T>A, c.1151T>G, c.1204G>A, c.1244T>C, and c.1250G>A) and two previously reported mutations (c.323-6G>A and c.916G>A). Each of the five novel mutations was classified as severe, by both age of onset and severity of hearing loss. Together with our previous study, six families were found to share one pathogenic mutation (c.916G>A, p.Ala306Thr). To determine whether this mutation arose from a common ancestor, we analyzed six short tandem repeat (STR) markers spanning the gene. In four families, we observed linkage disequilibrium between p.Ala306Thr and STR markers. Our results indicate that mutations in account for about 4.6% (7/151) of Chinese ARNSHL cases lacking mutations in or and that the recurrent mutation p.Ala306Thr is likely to be a founder mutation.