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

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.

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.

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.

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.