Next-generation sequencing identifies rare pathogenic and novel candidate variants in a cohort of Chinese patients with syndromic or nonsyndromic hearing loss.

Background: Hearing loss (HL) is a common sensory disorder in humans characterized by extreme clinical and genetic heterogeneity. In recent years, next-generation sequencing (NGS) technologies have proven to be highly effective and powerful tools for population genetic studies of HL. Here, we analyzed clinical and molecular data from 21 Chinese deaf families who did not have hotspot mutations in the common deafness genes GJB2, SLC26A4, GJB3, and MT-RNR1.

Method: Targeted next-generation sequencing (TGS) of 127 known deafness genes was performed in probands of 12 families, while whole-exome sequencing (WES) or trio-WES was used for the remaining nine families.

Results: Potential pathogenic mutations in a total of 12 deafness genes were identified in 13 probands; the mutations were observed in GJB2, CDH23, EDNRB, MYO15A, OTOA, OTOF, TBC1D24, SALL1, TMC1, TWNK, USH1C, and USH1G, with eight of the identified mutations being novel. Further, a copy number variant (CNV) was detected in one proband with heterozygous deletion of chromosome 4p16.3-4p15.32. Thus, the total diagnostic rate using NGS in our deafness patients reached 66.67% (14/21).

Conclusions: These results expand the mutation spectrum of deafness-causing genes and provide support for the use of NGS detection technologies for routine molecular diagnosis in Chinese deaf populations.