Novel compound heterozygous TMC1 mutations associated with autosomal recessive hearing loss in a Chinese family

Hereditary nonsyndromic hearing loss is highly heterogeneous and most patients with a presumed genetic etiology lack a specific diagnosis. It has been estimated that several hundred genes may be associated with this sensory deficit in humans. Here, we identified compound heterozygous mutations in th...

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Bibliographic Details
Published in:PloS one 2013-05, Vol.8 (5), p.e63026-e63026
Main Authors: Gao, Xue, Su, Yu, Guan, Li-Ping, Yuan, Yong-Yi, Huang, Sha-Sha, Lu, Yu, Wang, Guo-Jian, Han, Ming-Yu, Yu, Fei, Song, Yue-Shuai, Zhu, Qing-Yan, Wu, Jing, Dai, Pu
Format: Article
Language:English
Subjects:
Adolescent
Alleles
Amino Acid Sequence
Animals
Asian Continental Ancestry Group - genetics
Auditory defects
Base Sequence
Bioinformatics
Biology
Congenital diseases
Deoxyribonucleic acid
Development and progression
DNA
DNA Mutational Analysis
DNA sequencing
Etiology
Exome - genetics
Family
Female
Genes
Genetic aspects
Genetic testing
Genomes
Genomics
Hearing loss
Hearing Loss, Sensorineural - genetics
Hearing Loss, Sensorineural - pathology
Hearing Loss, Sensorineural - physiopathology
Hearing protection
Heterozygote
Humans
Male
Medicine
Membrane Proteins - chemistry
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Minority & ethnic groups
Missense mutation
Molecular Sequence Data
Mutation
Nonsense mutation
Otolaryngology
Patients
Pedigree
Polymorphism, Genetic
Rats
Siblings
Surgery
Young Adult
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Summary:Hereditary nonsyndromic hearing loss is highly heterogeneous and most patients with a presumed genetic etiology lack a specific diagnosis. It has been estimated that several hundred genes may be associated with this sensory deficit in humans. Here, we identified compound heterozygous mutations in the TMC1 gene as the cause of recessively inherited sensorineural hearing loss by using whole-exome sequencing in a family with two deaf siblings. Sanger sequencing confirmed that both siblings inherited a missense mutation, c.589G>A p.G197R (maternal allele), and a nonsense mutation, c.1171C>T p.Q391X (paternal allele), in TMC1. We also used DNA from 50 Chinese familial patients with ARNSHL and 208 ethnicity-matched negative samples to perform extended variants analysis. Both variants co-segregated in family 1953, which had the hearing loss phenotype, but were absent in 50 patients and 208 ethnicity-matched controls. Therefore, we concluded that the hearing loss in this family was caused by novel compound heterozygous mutations in TMC1.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0063026