Exome sequencing identifies a mutation in TMC1 as a novel cause of autosomal recessive nonsyndromic hearing loss

Journal of Translational Medicine
Jiongjiong HuZhaoxin Ma

Abstract

Autosomal recessive non-syndromic hearing loss (ARNSHL) is highly heterogeneous, and mutations in the gene encoding transmembrane channel-like 1 (TMC1) have been implicated in its development. To date, 35 homozygous mutations in TMC1, identified in over 60 families worldwide, have been shown to be associated with ARNSHL. However, few of these mutations were detected in the Chinese population. In this study, we describe a pathogenic missense mutation located in the T5-T6 domain of TMC1 in a three-generation Chinese family with 14 members. Whole exome sequencing was performed using samples from one unaffected individual and two affected individuals to systematically search for deafness susceptibility genes. Candidate mutations and cosegregation of the phenotype were verified by polymerase chain reaction and Sanger sequencing in all of the family members. We identified a novel TMC1 mutation in exon 20, c.1979C>T, p.P660L, which segregated with prelingual autosomal recessive sensorineural hearing loss. We found a new missense mutation in the T5-T6 domain of TMC1, which is highly conserved in many species. These data support the potential conserved role of p.P660L in human TMC1 function.

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Citations

Jul 15, 2016·Biophysical Journal·Robert Fettiplace
Mar 14, 2018·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Yi JiangPu Dai
Apr 15, 2018·Molecular Genetics & Genomic Medicine·Hongyang WangQiuju Wang
Oct 5, 2019·Cellular and Molecular Life Sciences : CMLS·Xiaomin YueRui Xiao

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Methods Mentioned

BETA
exome sequencing

Software Mentioned

MutationTaster
Clustal
Samtools
Polyphen2
SIFT

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