Mutations of human TMHS cause recessively inherited non-syndromic hearing loss
Mutations of human TMHS cause recessively inherited non-syndromic hearing loss
复制标题
DOI：
10.1136/jmg.2005.039834
复制
发表时间：
2006-08-01
影响因子：
4
通讯作者：
Riazuddin, Sheikh
中科院分区：
文献类型：
--
作者：
Shabbir, M. I.;Ahmed, Z. M.;Riazuddin, Sheikh
背景：大约一半的语前听力损失病例是由遗传因素引起的。识别导致耳聋的基因是了解这些基因在听觉系统中正常功能的关键第一步。最近，据报道，Tmhs 的突变等位基因与仓促小鼠的耳聋和绕圈行为有关。 Tmhs 编码一种功能未知的预测四跨蛋白，该蛋白在内耳毛细胞中表达。 Tmhs 的人类同源物位于染色体 6p 上。目的：确定四个近亲家庭的耳聋原因，这些家族分离隐性耳聋，这些隐性耳聋与染色体 6p21.1-p22.3 上的标记相关，定义了一个新的 DFNB 位点。结果：非综合征性耳聋 DFNB67 的一个新位点被定位在人类染色体上约 28.51 cM 的区间内。 6p21.1-p22.3。 TMHS 的 DNA 序列分析显示，两个非综合征性耳聋家族的受影响个体存在纯合移码突变 (246delC) 和错义突变 (Y127C)，其中之一显示出与 DFNB67 间隔中的标记连锁的显着证据。 mTMHS 在发育中的小鼠内耳毛细胞中的定位得到了完善，并发现从 E16.5 到 P3 短暂表达。结论：这些发现确立了 TMHS 对于人类正常声音转导的重要性。
Background: Approximately half the cases of prelingual hearing loss are caused by genetic factors. Identification of genes causing deafness is a crucial first step in understanding the normal function of these genes in the auditory system. Recently, a mutant allele of Tmhs was reported to be associated with deafness and circling behaviour in the hurry-scurry mouse. Tmhs encodes a predicted tetraspan protein of unknown function, which is expressed in inner ear hair cells. The human homologue of Tmhs is located on chromosome 6p.Objective: To determine the cause of deafness in four consanguineous families segregating recessive deafness linked to markers on chromosome 6p21.1-p22.3 defining a novel DFNB locus.Results: A novel locus for non-syndromic deafness DFNB67 was mapped in an interval of approximately 28.51 cM on human chromosome 6p21.1-p22.3. DNA sequence analysis of TMHS revealed a homozygous frameshift mutation (246delC) and a missense mutation (Y127C) in affected individuals of two families segregating non-syndromic deafness, one of which showed significant evidence of linkage to markers in the DFNB67 interval. The localisation of mTMHS in developing mouse inner ear hair cells was refined and found to be expressed briefly from E16.5 to P3.Conclusions: These findings establish the importance of TMHS for normal sound transduction in humans.