Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function

Nat Genet. 2002 Mar;30(3):277-84. doi: 10.1038/ng842. Epub 2002 Feb 19.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Chromosome Mapping
  • Chromosomes, Human, Pair 9
  • Deafness / genetics*
  • Female
  • Genes, Dominant*
  • Genes, Recessive*
  • Hair Cells, Auditory / physiopathology*
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Multigene Family
  • Mutation*
  • Pedigree
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid


  • Membrane Proteins
  • RNA, Messenger
  • TMC1 protein, human