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- Title
Exome sequencing identifies a mutation in TMC1 as a novel cause of autosomal recessive nonsyndromic hearing loss.
- Authors
Jiongjiong Hu; Fei Liu; Wenjun Xia; Lili Hao; Jun Lan; Zhenghua Zhu; Jing Ye; Duan Ma; Zhaoxin Ma; Hu, Jiongjiong; Liu, Fei; Xia, Wenjun; Hao, Lili; Lan, Jun; Zhu, Zhenghua; Ye, Jing; Ma, Duan; Ma, Zhaoxin
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>We identified a novel TMC1 mutation in exon 20, c.1979C>T, p.P660L, which segregated with prelingual autosomal recessive sensorineural hearing loss.<bold>Conclusions: </bold>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.
- Subjects
EXOMES; DIAGNOSIS of deafness; GENES; GENETIC mutation; MEMBRANE proteins; AMINO acids; ASIANS; AUDIOMETRY; COMPUTER simulation; HEARING disorders; DISEASE susceptibility; DOCUMENTATION; FAMILIES; GENEALOGY; GENETIC polymorphisms; GENETIC techniques; GENOMES; NUCLEOTIDES; PHENOTYPES; SEQUENCE analysis
- Publication
Journal of Translational Medicine, 2016, Vol 14, p1
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/s12967-016-0780-5