Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function
Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function
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DOI：
10.1038/ng842
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发表时间：
2002-03-01
期刊：
影响因子：
30.8
通讯作者：
Griffith, AJ
中科院分区：
文献类型：
--
作者：
Kurima, K;Peters, LM;Griffith, AJ
遗传性耳聋基因的位置克隆是识别听觉功能分子和机制的直接方法。在这里，我们报告了显性耳聋的基因座 DFNA36，它映射到人类染色体 9q13-21 的区域，与隐性耳聋的 DFNB7/B11 基因座重叠。我们在 DFNA36 家族和 11 个 DFNB7/B11 家族中发现了新基因跨膜耳蜗表达基因 1 (TMC1) 的 8 个突变。我们在隐性耳聋 (dn) 小鼠突变体中检测到包含 Tmc1 外显子 14 的 1.6 kb 基因组缺失，该突变体缺乏听觉反应并具有毛细胞变性(1,2)。染色体 20p13 上的 TMC1 和 TMC2 是预计编码跨膜蛋白的基因家族的成员。 Tmc1 mRNA 在出生后小鼠耳蜗和前庭终末器官的毛细胞中表达，是耳蜗毛细胞正常功能所必需的。
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). 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.