Nature Genetics
30, 277 - 284 (2002)
Published online: 19 February 2002; | doi:10.1038/ng842
Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell functionKiyoto Kurima1, Linda M. Peters2, Yandan Yang1, Saima Riazuddin2, Zubair M. Ahmed2, 3, Sadaf Naz2, Deidre Arnaud4, Stacy Drury4, Jianhong Mo2, Tomoko Makishima1, Manju Ghosh5, P.S.N. Menon5, Dilip Deshmukh6, Carole Oddoux7, Harry Ostrer7, Shaheen Khan3, Sheikh Riazuddin3, Prescott L. Deininger8, Lori L. Hampton9, Susan L. Sullivan10, James F. Battey Jr.9, Bronya J.B. Keats4, Edward R. Wilcox2, Thomas B. Friedman2
& Andrew J. Griffith1, 111
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. 2
Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, Maryland 20850, USA. 3
Center of Excellence in Molecular Biology, Punjab University, Thokar Niaz Baig, Lahore, Pakistan. 4
Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. 5
Genetics Unit, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. 6
Rotary Deaf School, Ichalkaranji-Tilawani, Maharashtra, India. 7
Human Genetics Program, Department of Pediatrics, New York University School of Medicine, New York, New York, USA. 8
Department of Environmental Health Sciences, Tulane University Medical Center, New Orleans, Louisiana, USA. 9
G-protein Coupled Receptors' Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 50 Center Drive, Bethesda, Maryland, USA. 10
Section on Molecular Neuroscience, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, Maryland 20850, USA. 11
Hearing Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, Maryland 20850, USA.
Correspondence should be addressed to Andrew J. Griffith griffita@nidcd.nih.govPositional 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 degeneration1,
2. 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.
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