Genetic etiology study of the non-syndromic deafness in Chinese Hans by targeted next-generation sequencing

Background: Although over 60 non-syndromic deafness genes have been identified to date, the etiologic contribution of most deafness genes remained elusive. In this study, we addressed this issue by targeted next-generation sequencing of a large cohort of non-syndromic deaf probands. Methods: Probands with mutations in commonly screened deafness genes GJB2, SLC26A4 and MT-RNR1 were pre-excluded by Sanger sequencing. The remaining 125 deaf probands proceeded through targeted exon capturing of 79 known deafness genes and Illumina HiSeq2000 sequencing. Results: Bi-allelic mutations in 15 less commonly screened deafness genes were identified in 28 deaf probands, with mutations in MYO15A, GPR98, TMC1, USH2A and PCDH15 being relatively more frequent (>= 3 probands each). Dominant mutations in MYO6, TECTA, POU4F3 and COCH were identified in 4 deaf families. A mitochondrial MTTS1 mutation was identified in one maternally inherited deaf family. No pathogenic mutations were identified in three dominant deaf families and two consanguineous families. Conclusions: Mutations in the less commonly screened deafness genes were heterogeneous and contributed to a significant percentage (17.4%) of causes for non-syndromic deafness. Targeted next-generation sequencing provided a comprehensive and efficient diagnosis for known deafness genes. Complementary to linkage analysis or whole-exome sequencing of deaf families, pre-exclusion of known deafness genes by this strategy may facilitate the discovery of novel deafness genes.