title: Exome sequencing identifies a mutation in TMC1 as a novel cause of autosomal recessive nonsyndromic hearing loss.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  We identified a novel TMC1 mutation in exon 20, c.1979C>T, p.P660L, which segregated with prelingual autosomal recessive sensorineural hearing loss.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, 200032, People's Republic of China. hujiongjiong@vip.sina.com.
authors.forename: Jiongjiong
authors.initials: J
authors.lastname: Hu
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People's Republic of China. feilion_01@hotmail.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People's Republic of China. 14111510032@fudan.edu.cn.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xia
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People's Republic of China. haoli2010happy@163.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, 200032, People's Republic of China. lj0312@easthospital.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Lan
authors.affiliation: Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, 200032, People's Republic of China. brother.fd@163.com.
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, 200032, People's Republic of China. yilia_yejing@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Molecular Biology, Institute of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People's Republic of China. duanma@fudan.edu.cn.|Institutes of Biomedical Science, Fudan University, Shanghai, 200032, People's Republic of China. duanma@fudan.edu.cn.
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, 200032, People's Republic of China. mzhx163@hotmail.com.
authors.forename: Zhaoxin
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People; D001299:Audiometry; D001483:Base Sequence; D003198:Computer Simulation; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics*; D059472:Exome; D005190:Family; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C451751:TMC1 protein, human
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