de Heer Anne-Martine R, Collin Rob W J, Huygen Patrick L M, Schraders Margit, Oostrik Jaap, Rouwette Myrthe, Kunst Henricus P M, Kremer Hannie, Cremers Cor W R J
Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Audiol Neurootol. 2011;16(2):93-105. doi: 10.1159/000313282. Epub 2010 Jun 26.
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.
在一个患有常染色体隐性遗传性听力损失的荷兰家庭中，全基因组单核苷酸多态性分析将基因缺陷定位到DFNB7/11位点。在第19号内含子的剪接供体位点附近检测到TMC1基因中一个新的纯合A到G的变化（c.1763+3A→G），该变化与这个家庭的听力损失共分离。预测突变蛋白中6个跨膜结构域之一和实际的TMC通道结构域缺失。这个DFNB7/11家庭的感音神经性听力障碍在语言发育后发病。听力测定分析最初显示阈值构型急剧向下倾斜。这个家庭的进行性表型类似于先前描述的具有显性TMC1突变的家庭（DFNA36），而不是具有隐性TMC1突变的家庭（DFNB7/11）的表型，后者总是导致严重至极重度的语言前听力障碍。
