title: Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function.
abstract: Positional cloning of hereditary deafness genes is a direct approach to identify molecules and mechanisms underlying auditory function. Here we report a locus for dominant deafness, DFNA36, which maps to human chromosome 9q13-21 in a region overlapping the DFNB7/B11 locus for recessive deafness. We identified eight mutations in a new gene, transmembrane cochlear-expressed gene 1 (TMC1), in a DFNA36 family and eleven DFNB7/B11 families. We detected a 1.6-kb genomic deletion encompassing exon 14 of Tmc1 in the recessive deafness (dn) mouse mutant, which lacks auditory responses and has hair-cell degeneration. TMC1 and TMC2 on chromosome 20p13 are members of a gene family predicted to encode transmembrane proteins. Tmc1 mRNA is expressed in hair cells of the postnatal mouse cochlea and vestibular end organs and is required for normal function of cochlear hair cells.
authors.affiliation: Section on Gene Structure and Function, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, Maryland 20850, USA.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kurima
authors.forename: Linda M
authors.initials: LM
authors.lastname: Peters
authors.forename: Yandan
authors.initials: Y
authors.lastname: Yang
authors.forename: Saima
authors.initials: S
authors.lastname: Riazuddin
authors.forename: Zubair M
authors.initials: ZM
authors.lastname: Ahmed
authors.forename: Sadaf
authors.initials: S
authors.lastname: Naz
authors.forename: Deidre
authors.initials: D
authors.lastname: Arnaud
authors.forename: Stacy
authors.initials: S
authors.lastname: Drury
authors.forename: Jianhong
authors.initials: J
authors.lastname: Mo
authors.forename: Tomoko
authors.initials: T
authors.lastname: Makishima
authors.forename: Manju
authors.initials: M
authors.lastname: Ghosh
authors.forename: P S N
authors.initials: PS
authors.lastname: Menon
authors.forename: Dilip
authors.initials: D
authors.lastname: Deshmukh
authors.forename: Carole
authors.initials: C
authors.lastname: Oddoux
authors.forename: Harry
authors.initials: H
authors.lastname: Ostrer
authors.forename: Shaheen
authors.initials: S
authors.lastname: Khan
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
authors.forename: Prescott L
authors.initials: PL
authors.lastname: Deininger
authors.forename: Lori L
authors.initials: LL
authors.lastname: Hampton
authors.forename: Susan L
authors.initials: SL
authors.lastname: Sullivan
authors.forename: James F
authors.initials: JF
authors.lastname: Battey
authors.forename: Bronya J B
authors.initials: BJ
authors.lastname: Keats
authors.forename: Edward R
authors.initials: ER
authors.lastname: Wilcox
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D003638:Deafness / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D006198:Hair Cells, Auditory / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; C451751:TMC1 protein, human