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

Kiyoto Kurima, Linda M. Peters, Yandan Yang, Saima Riazuddin, Zubair M. Ahmed, Sadaf Naz, Deidre Arnaud, Stacy Drury, Jianhong Mo, Tomoko Makishima, Manju Ghosh, P. S.N. Menon, Dilip Deshmukh, Carole Oddoux, Harry Ostrer, Shaheen Khan, Sheikh Riazuddin, Prescott L. Deininger, Lori L. Hampton, Susan L. SullivanJames F. Battey, Bronya J.B. Keats, Edward R. Wilcox, Thomas B. Friedman, Andrew J. Griffith

Research output: Contribution to journalArticle

258 Scopus citations

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 1, 2. TMO 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 reqired for normal function of cochlear hair cells.

Original languageEnglish (US)
Pages (from-to)277-284
Number of pages8
JournalNature Genetics
Volume30
Issue number3
DOIs
StatePublished - Mar 2002
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function'. Together they form a unique fingerprint.

  • Cite this

    Kurima, K., Peters, L. M., Yang, Y., Riazuddin, S., Ahmed, Z. M., Naz, S., Arnaud, D., Drury, S., Mo, J., Makishima, T., Ghosh, M., Menon, P. S. N., Deshmukh, D., Oddoux, C., Ostrer, H., Khan, S., Riazuddin, S., Deininger, P. L., Hampton, L. L., ... Griffith, A. J. (2002). Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function. Nature Genetics, 30(3), 277-284. https://doi.org/10.1038/ng842