Abstract
Hearing impairment is the most commonly occurring condition that affects the ability of humans to communicate 1 . More than 50% of the cases of profound early-onset deafness are caused by genetic factors 2, 3 . Over 40 loci for non-syndromic deafness have been genetically mapped, and mutations in several genes have been shown to cause hearing loss 4 . Mutations in the gene encoding connexin 26 ( GJB2 ) cause both autosomal recessive and dominant forms of hearing impairment 5, 6 . To study the possible involvement of other members of the connexin family in hereditary hearing impairment, we cloned the gene ( GJB3 ) encoding human gap junction protein β-3 using homologous EST searching and nested PCR. GJB3 was mapped to human chromosome 1p33-p35. Mutation analysis revealed that a missense mutation and a nonsense mutation of GJB3 were associated with high-frequency hearing loss in two families. Moreover, expression of Gjb3 was identified in rat inner ear tissue by RT-PCR. These findings suggest that mutations in GJB3 may be responsible for bilateral high-frequency hearing impairment.
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References
Morton, N.E. Genetic epidemiology of hearing impairment. Ann. N.Y. Acad. Sci . 630, 16–31 ( 1991).
Marazita, M.L. et al. Genetic epidemiological studies of early-onset deafness in the U.S. school-age population. Am. J. Med. Genet. 46, 486–491 (1993).
Reardon, W. Genetic deafness. J. Med. Genet. 29, 521 –526 (1992).
Van Camp, G., Willems, P.J. & Smith, R.J.H. Non-syndromic hearing impairment: unparalleled heterogeneity. Am. J. Hum. Genet. 60, 758– 764 (1997).
Denoyelle, F. et al. Connexin 26 gene linked to a dominant deafness. Nature 393, 319–320 ( 1998).
Kelsell, D.P. et al. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 387, 80– 83 (1997).
Bergoffen, J. et al. Connexin mutations in X-linked Charcot-Marie-Tooth disease. Science 262, 2039–2042 (1993).
Coucke, P. et al. Linkage of autosomal dominant hearing loss to the short arm of chromosome 1 in two families. N. Engl. J. Med. 331, 425–431 (1994).
Van Camp, G. et al. Linkage analysis of progressive hearing loss in five extended families maps the DFNA2 gene to a 1.25-Mb region on chromosome 1p. Genomics 41, 70–74 ( 1997).
van der Schroeff, J.G., van Leeuwen-Cornelisse, I., van Haeringen, A. & Went, L.N. Further evidence for localization of the gene of erythrokeratodermia variabilis. Hum. Genet. 80, 97–98 (1998).
Ben Othmane, K. et al. Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity. Genomics 17, 370– 375 (1993).
Engle, E.C., Castro, A.E., Macy, M.E., Knoll, J.H. & Beggs, A.H. A gene for isolated congenital ptosis maps to a 3-cM region within 1p32-p34.1. Am. J. Hum. Genet. 60, 1150–1157 (1997).
Kelley, P.M. et al. Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss. Am. J. Hum. Genet. 62, 792–799 ( 1998).
Fain, P.R., Barker, D.F. & Chance, P.F. Refined genetics mapping of X-linked Charcot-Marie-Tooth neuropathy. Am. J. Hum. Genet. 54, 229– 235 (1994).
Scott, D.A., Kraft, M.L., Stone, E.M., Sheffield, V.C. & Smith, R.J. Connexin mutations and hearing loss. Nature 391, 32 (1998).
White, T.W., Deans, M.R., Kelsell, D.P. & Paul, D.L. Connexin mutation in deafness. Nature 394, 630–631 (1988).
Ayimu, D. & Qiu, C. Pure tone threshold in 5000 normal ears. J. Audiol. Speech Pathol. 5, 144– 145 (1997).
Hull, R.H. Hearing evaluation of the elderly. in Handbook of Clinical Audiology (ed. Katz, J. ) 426–441 (Williams & Wilkins, Baltimore, 1978).
Elgoyhen, A.B., Johnson, D.S., Boulter, J., Vetter, D.E. & Heinemann, S. α9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells. Cell 79, 705–715 (1994).
Acknowledgements
This study was supported by a Chinese 863 projects grant (z19-02-02-02), the Chinese Natural Science Foundation (grant 39392902) and SmithKline Beecham-Hunan Medical University Collaborative Project.
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Xia., Jh., Liu, Cy., Tang, Bs. et al. Mutations in the gene encoding gap junction protein β-3 associated with autosomal dominant hearing impairment. Nat Genet 20, 370–373 (1998). https://doi.org/10.1038/3845
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DOI: https://doi.org/10.1038/3845
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