title: Novel compound heterozygous TMC1 mutations associated with autosomal recessive hearing loss in a Chinese family.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Su
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Guan
authors.forename: Yong-Yi
authors.initials: YY
authors.lastname: Yuan
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Huang
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
authors.forename: Guo-Jian
authors.initials: GJ
authors.lastname: Wang
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Han
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.forename: Yue-Shuai
authors.initials: YS
authors.lastname: Song
authors.forename: Qing-Yan
authors.initials: QY
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D011110:Polymorphism, Genetic; D051381:Rats; D035781:Siblings; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C451751:TMC1 protein, human