Identification ofTMPRSS3as 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 theTMPRSS3(transmembrane protease, serine 3) gene cause prelingual (DFNB10) or postlingual (DFNB8) deafness. In our previous study, three pathogenic mutations inTMPRSS3were identified in one Chinese family. To evaluate the importance ofTMPRSS3mutations in recessive deafness among the Chinese, we screened 150 autosomal recessive nonsyndromic hearing loss (ARNSHL) families and identified 6 that carried seven causativeTMPRSS3mutations, 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 theTMPRSS3gene. In four families, we observed linkage disequilibrium between p.Ala306Thr and STR markers. Our results indicate that mutations inTMPRSS3account for about 4.6% (7/151) of Chinese ARNSHL cases lacking mutations inSLC26A4orGJB2and that the recurrentTMPRSS3mutation p.Ala306Thr is likely to be a founder mutation.