Mutation analysis of TMC1 identifies four new mutations and suggests an additional deafness gene at loci DFNA36 and DFNB7/11.
Mutation analysis of TMC1 identifies four new mutations and suggests an additional deafness gene at loci DFNA36 and DFNB7/11.
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TMC1的突变分析鉴定了四个新突变，并提出了位点DFNA36和DFNB7/11的额外耳聋基因。
DOI：
10.1111/j.1399-0004.2008.01053.x
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发表时间：
2008-09
影响因子：
3.5
通讯作者：
Van Camp G
中科院分区：
文献类型：
--
作者：
Hilgert N;Alasti F;Dieltjens N;Pawlik B;Wollnik B;Uyguner O;Delmaghani S;Weil D;Petit C;Danis E;Yang T;Pandelia E;Petersen MB;Goossens D;Favero JD;Sanati MH;Smith RJ;Van Camp G
听力损失是最常见的感觉神经性疾病，每1000名新生儿中就有1名受到影响。在这些婴儿中，超过一半的听力损失是遗传的。遗传性听力损失是一个非常异质性的性状，大约有100个基因定位和44个基因鉴定的非综合征性听力损失。TMC 1已被确定为常染色体显性和常染色体隐性非综合征性听力损失的致病基因，分别位于DFNA 36和DFNB 7/11位点。迄今为止，已有34个家庭报告了2种显性和18种隐性TMC 1突变是导致听力损失的原因。在这份报告中，我们描述了一个显性和10个隐性非综合征感音神经性耳聋家系与DFNA 36和DFNB 7/11的连锁。此外，在51例常染色体隐性遗传性听力损失的家族性土耳其患者中进行了TMC 1的突变分析。在七个隐性听力损失分离家庭中发现了TMC 1突变。我们发现的致病性变异包括两个已知的突变，c.100C>T和c.1165C>T，以及四个新的突变，c.2350C>T，c.776+1G>A，c.767_768del和c.1166G>A。在其余6个连锁家族中不存在TMC 1突变意味着该基因编码区以外存在突变，或者该区域中存在至少一个额外的致突变基因。对TMC 1拷贝数变异的分析以及对另外15个候选基因的DNA测序没有发现任何已证实的致病性变化，这两种假设都是开放的。
Hearing loss is the most frequent sensorineural disorder, affecting 1 in 1000 newborns. In more than half of these babies, the hearing loss is inherited. Hereditary hearing loss is a very heterogeneous trait, with about 100 gene localizations and 44 gene identifications for nonsyndromic hearing loss. TMC1 has been identified as the disease-causing gene for autosomal dominant and autosomal recessive nonsyndromic hearing loss at the DFNA36 and DFNB7/11 loci, respectively. To date, two dominant and 18 recessive TMC1 mutations have been reported as the cause of hearing loss in 34 families. In this report, we describe linkage to DFNA36 and DFNB7/11 in one family with dominant and 10 families with recessive nonsyndromic sensorineural hearing loss. In addition, mutation analysis of TMC1 was performed in 51 familial Turkish patients with autosomal recessive hearing loss. TMC1 mutations were identified in seven of the families segregating recessive hearing loss. The pathogenic variants we found included two known mutations, c.100C>T and c.1165C>T, and four new mutations, c.2350C>T, c.776+1G>A, c.767_768del and c.1166G>A. The absence of TMC1 mutations in the remaining six linked families implies the presence of mutations outside the coding region of this gene, or alternatively, at least one additional deafness-causing gene in this region. The analysis of copy number variations in TMC1 as well as DNA sequencing of 15 additional candidate genes did not reveal any proven pathogenic changes, leaving both hypotheses open.