Mutation screening in non-syndromic hearing loss patients with cochlear implantation by massive parallel sequencing in Taiwan

Abstract

Objectives To explore the molecular epidemiology of rare deafness genes in Taiwanese sensorineural hearing impairment (SNHI) patients with cochlear implantation (CI) by performing massive parallel sequencing (MPS) and correlating genetic factors and CI outcomes. Methods We enrolled 41 Taiwanese non-syndromic deafness patients with CI that lacked known mutations in common deafness genes. All probands were screened by a targeted exon amplification method that used massively parallel sequencing to screen a customized panel that included 40 relatively rare non-syndromic deafness genes. Results Thirteen candidate variants in nine relatively rare deafness genes (MYO15A, TMC1, MYH14, MYO3A, ACTG1, COL11A2, DSPP, GRHL2, and WFS1) were identified in 24.4% (10/41) of the non-syndromic deafness probands with CI. According to the ACMG Standards and Guidelines, five variants in MYO15A and ACTG1 were classified as likely pathogenic variants. Two of three multi-generational pedigrees exhibiting deafness were analyzed for the segregation of the disorder with the possible disease-causing variants. Patients with variants detected in most of the identified variant-bearing genes showed relatively good CI outcomes. Conclusions We successfully identified candidate variants in partially deaf Taiwanese probands who lacked the known mutations in common deafness genes. Comparing the progress of hearing rehabilitation in CI patients with their apparent causative variants and the expression profiles of their altered genes allowed us to speculate on how alterations in specific gene sets may influence outcomes in hearing rehabilitation after CI.