Progressive Sensorineural Hearing Loss and Normal Vestibular Function in a Dutch DFNB7/11 Family with a Novel Mutation in TMC1
Progressive Sensorineural Hearing Loss and Normal Vestibular Function in a Dutch DFNB7/11 Family with a Novel Mutation in TMC1
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DOI：
10.1159/000313282
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发表时间：
2011-01-01
影响因子：
1.6
通讯作者：
Cremers, Cor W. R. J.
中科院分区：
文献类型：
--
作者：
de Heer, Anne-Martine R.;Collin, Rob W. J.;Cremers, Cor W. R. J.
在一个荷兰常染色体隐性遗传性听力损失家族中，全基因组单核苷酸多态性分析将遗传缺陷定位于DFNB 7/11位点。在TMC 1基因第19内含子的剪接供体位点（c.1763+3A-->G）附近检测到一种新的纯合性A-G改变，与该家系的听力损失分离。预测突变蛋白中不存在6个跨膜结构域之一和实际TMC通道结构域。DFNB 7/11家族的感音神经性听力障碍是在语后发病的。听力测定分析最初显示了一个陡峭的向下倾斜的阈值配置。该家族的进行性表型类似于先前描述的显性TMC 1突变（DFNA 36）家族的表型，而不是隐性TMC 1突变（DFNB 7/11）家族的表型，隐性TMC 1突变总是导致严重至极深的语前听力障碍。版权所有（C）2010 S. Karger AG，巴塞尔
In a Dutch family with autosomal recessive hearing loss, genome-wide single-nucleotide polymorphism analysis mapped the genetic defect to the DFNB7/11 locus. A novel homozygous A-to-G change in the TMC1 gene was detected near the splice donor site of intron 19 (c.1763+3A-->G) segregating with the hearing loss in this family. One of the 6 transmembrane domains and the actual TMC channel domain are predicted to be absent in the mutant protein. The sensorineural hearing impairment in this DFNB7/11 family has a postlingual onset. Audiometric analysis initially showed a steeply downward-sloping threshold configuration. The progressive phenotype in this family resembles the phenotype previously described for families with dominant TMC1 mutations (DFNA36) rather than that of families with recessive TMC1 mutations (DFNB7/11) which invariably cause severe-to-profound prelingual hearing impairment. Copyright (C) 2010 S. Karger AG, Basel