Whole-exome sequencing identifies MYO15A mutations as a cause of autosomal recessive nonsyndromic hearing loss in Korean families

Hae-Mi Woo,Mi-Hyun Park,Jeong-In Baek,Borum Sagong,Un-Kyung Kim,Soo Kyung Koo,Hong-Joon Park

doi:10.1186/1471-2350-14-72

Abstract

BackgroundThe genetic heterogeneity of hearing loss makes genetic diagnosis expensive and time consuming using available methods. Whole-exome sequencing has recently been introduced as an alternative approach to identifying causative mutations in Mendelian disorders.MethodsTo identify the hidden mutations that cause autosomal recessive nonsyndromic hearing loss (ARNSHL), we performed whole-exome sequencing of 13 unrelated Korean small families with ARNSHL who were negative for GJB2 or SLC26A4 mutations.ResultsWe found two novel compound heterozygous mutations, IVS11 + 1 and p.R2146Q, of MYO15A in one (SR903 family) of the 13 families with ARNSHL. In addition to these causative mutations, 13 nonsynonymous variants, including variants with uncertain pathogenicity (SR285 family), were identified in the coding exons of MYO15A from Korean exomes.ConclusionThis is the first report of MYO15A mutations in an East Asian population. We suggest that close attention should be paid to this gene when performing genetic testing of patients with hearing loss in East Asia. The present results also indicate that whole-exome sequencing is a valuable method for comprehensive medical diagnosis of a genetically heterogeneous recessive disease, especially in small-sized families.

Highlights

The genetic heterogeneity of hearing loss makes genetic diagnosis expensive and time consuming using available methods
Probands from each family were found to be negative for GJB2 and SLC26A4 mutations based on Sanger sequencing
Whole-exome sequencing We performed whole-exome sequencing of 16 individuals from 13 unrelated families with autosomal recessive nonsyndromic hearing loss (ARNSHL), and found compound heterozygous mutations in the MYO15A gene from the SR-903 family, as well as a novel variant in the same gene from the SR-285 family (Additional file 1: Figure S1)

Summary

Introduction

The genetic heterogeneity of hearing loss makes genetic diagnosis expensive and time consuming using available methods. The genes that are most commonly implicated in ARNSHL are in order of frequency: GJB2, SLC26A4, MYO15A, OTOF, and CDH23 [2]. Mutations in these genes do not occur at the same frequencies across ethnicities. The current genetic diagnosis of hearing loss is limited to common mutations in a patient’s population of origin and relies on a gene-specific Sanger sequencing approach. This method is useful in some populations. In East Asian populations, GJB2 is responsible for a much lower percentage of deafness cases, and other genes associated with this disease remain largely unknown [4]

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Discussion

Conclusion