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

Date Published: January 25, 2019

Publisher: Public Library of Science

Author(s): Wei-Hsiu Liu, Pi-Yueh Chang, Shih-Cheng Chang, Jang-Jih Lu, Che-Ming Wu, Namik Kaya.

http://doi.org/10.1371/journal.pone.0211261

Abstract

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.

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.

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.

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.

Partial Text

Sensorineural hearing impairment (SNHI) is a common clinical disorder that severely to profoundly affects at least 1 in 1000 children of developed countries [1]. Cochlear implantation (CI) is currently regarded as the standard treatment for severe to profound SNHI in children. CI has well-documented benefits for spoken language, reading skills, and cognitive development [2], but the outcomes after CI can vary among individuals. Age at implantation [3, 4], residual hearing [5], the presence of inner ear malformations [6], the presence of cochlear nerve deficiency [7], parent-child interactions [2], and socioeconomic status [2] have all been shown to affect the outcomes.

In the present study, we sought to clarify the genetic characteristics of non-syndromic deafness patients without the known mutations in common deafness-related genes. Using MPS, we successfully identified candidate variants in 24.4% of these patients (10/41) by targeting 40 relatively less common and non-syndromic hearing loss genes. We also examined the segregation of the potential disease-causing variants in the families of two multiplex probands. Among the patients harboring the identified candidate variants, eight showed good CI outcomes, while two showed poor outcomes.

 

Source:

http://doi.org/10.1371/journal.pone.0211261

 

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