title: Mutations of TMC1 cause deafness by disrupting mechanoelectrical transduction.
abstract: OBJECTIVE
  Mutations of transmembrane channel-like 1 gene (TMC1) can cause dominant (DFNA36) or recessive (DFNB7/B11) deafness. In this article, we describe the characteristics of DFNA36 and DFNB7/B11 deafness, the features of the Tmc1 mutant mouse strains, and recent advances in our understanding of TMC1 function.
  
  
  METHODS
  Publications related to TMC1, DFNA36, or DFNB7/B11 were identified through PubMed.
  
  
  RESULTS
  All affected DFNA36 subjects showed post-lingual, progressive, sensorineural hearing loss (HL), initially affecting high frequencies. In contrast, almost all affected DFNB7/B11 subjects demonstrated congenital or prelingual severe to profound sensorineural HL. The mouse Tmc1 gene also has dominant and recessive mutant alleles that cause HL in mutant strains, including Beethoven, deafness, and Tmc1 knockout mice. These mutant mice have been instrumental for revealing that Tmc1 and its closely related paralog Tmc2 are expressed in cochlear and vestibular hair cells, and are required for hair cell mechanoelectrical transduction (MET). Recent studies suggest that TMC1 and TMC2 may be components of the long-sought hair cell MET channel.
  
  
  CONCLUSIONS
  TMC1 mutations disrupt hair cell MET.
authors.affiliation: Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, 35A Convent Dr, Bethesda, MD 20892, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, 35A Convent Dr, Bethesda, MD 20892, USA.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kurima
authors.affiliation: Department of Otolaryngology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kawashima
authors.affiliation: Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, 35A Convent Dr, Bethesda, MD 20892, USA. Electronic address: griffita@nidcd.nih.gov.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
mesh_terms: D000818:Animals; D003638:Deafness / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000502:physiology; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009154:Mutation
chemical_list: D008565:Membrane Proteins; C451751:TMC1 protein, human; C514628:TMC1 protein, mouse
keywords: DFNA36; DFNB7/B11; Hearing loss; Mechanoelectrical transduction; TMC1; TMC2