title: Targeted gene capture and massively parallel sequencing identify TMC1 as the causative gene in a six-generation Chinese family with autosomal dominant hearing loss.
abstract: Hereditary nonsyndromic hearing loss is extremely heterogeneous. Mutations in the transmembrane channel-like gene1 (TMC1) are known to cause autosomal dominant and recessive forms of nonsyndromic hearing loss linked to the loci of DFNA36 and DFNB7/11, respectively. We characterized a six-generation Chinese family (5315) with progressive, postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining targeted capture of 82 known deafness genes, next-generation sequencing and bioinformatic analysis, we identified TMC1 c.1714G>A (p. D572N) as the disease-causing mutation. This mutation co-segregated with hearing loss in other family members and was not detected in 308 normal controls. In order to determine the prevalence of TMC1 c.1714G>A in Chinese ADNSHL families, we used DNA samples from 67 ADNSHL families with sloping audiogram and identified two families carry this mutation. To determine whether it arose from a common ancestor, we analyzed nine STR markers. Our results indicated that TMC1 c.1714G>A (p.D572N) account for about 4.4% (3/68) of ADNSHL in the Chinese population.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.|Department of Otolaryngology, Hainan Branch of PLA General Hospital, Sanya, P. R. China.|Department of Otorhinolaryngology, Second Artillery General Hospital, Beijing, P. R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Huang
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
authors.forename: Yong-Yi
authors.initials: YY
authors.lastname: Yuan
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.|Department of Otolaryngology, Hainan Branch of PLA General Hospital, Sanya, P. R. China.
authors.forename: Guo-Jian
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology, Second Artillery General Hospital, Beijing, P. R. China.
authors.forename: Jin-Cao
authors.initials: JC
authors.lastname: Xu
authors.affiliation: Department of Otorhinolaryngology, Second Artillery General Hospital, Beijing, P. R. China.
authors.forename: Yu-Bin
authors.initials: YB
authors.lastname: Ji
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.|Department of Otolaryngology, Hainan Branch of PLA General Hospital, Sanya, P. R. China.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Han
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
authors.forename: Dong-Yang
authors.initials: DY
authors.lastname: Kang
authors.affiliation: Department of Otolaryngology, Emory University School of Medicine, Atlanta, GA.
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.|Department of Otolaryngology, Hainan Branch of PLA General Hospital, Sanya, P. R. China.
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
mesh_terms: D000328:Adult; D044466:Asian People; D001299:Audiometry; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D019295:Computational Biology / Q000379:methods*; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D005799:Genes, Dominant; D056426:Genetic Loci; D005819:Genetic Markers; D006319:Hearing Loss, Sensorineural / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
chemical_list: D005819:Genetic Markers; D008565:Membrane Proteins; C451751:TMC1 protein, human
keywords: TMC1; autosomal dominant nonsyndromic hearing loss; massively parallel sequencing; targeted gene capture