Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene
Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene
复制标题
DOI：
10.1093/hmg/6.12.2173
复制
发表时间：
1997-11-01
影响因子：
3.5
通讯作者：
Petit, C
中科院分区：
文献类型：
--
作者：
Denoyelle, F;Weil, D;Petit, C
语前非综合征性（孤立性）耳聋是最常见的遗传性感觉缺陷。在超过 80% 的病例中，传播方式为常染色体隐性遗传。迄今为止，已鉴定出 14 个隐性基因座（DFNB 基因座）。对于其中的两个 DFNB1 和 DFNB2，相关基因已得到表征；它们分别编码连接蛋白 26 和肌球蛋白 VIIA。为了评估连接蛋白 26 基因 (Cx26) 对语前耳聋的影响程度，我们在来自不同国家（主要是突尼斯、法国、新西兰和英国）的 65 个受影响的白人家庭中搜索了该基因的突变。其中 6 个家族是近亲婚配，耳聋被证明与 DFNB1 基因座有关，10 个是小型非近亲婚配家族，其中性状的分离被发现与 DFNB1 的参与相容，而在其余 49 个家族中，未进行连锁分析。共鉴定出39个家族的62个突变等位基因。因此，Cx26 突变是隐性遗传性语前耳聋的主要原因，因为根据目前的结果，大约一半的病例是由这些突变引起的。此外，一种特定突变 30delG 占 Cx26 突变等位基因的大部分（约 70%）。因此，它是迄今为止发现的最常见的疾病突变之一。多项证据表明，30delG 突变的高患病率源于突变热点，而不是创始人效应。迄今为止，由于在有一个聋儿的家庭中难以区分遗传性和非遗传性耳聋，对语前耳聋的遗传咨询受到了很大的损害。根据这里提出的结果，可以设计一个简单的分子测试的开发，这应该有很大的帮助。
Prelingual non-syndromic (isolated) deafness is the most frequent hereditary sensory defect. In >80% of the cases, the mode of transmission is autosomal recessive. To date, 14 loci have been identified for the recessive forms (DFNB loci). For two of them, DFNB1 and DFNB2, the genes responsible have been characterized; they encode connexin 26 and myosin VIIA, respectively. In order to evaluate the extent to which the connexin 26 gene (Cx26) contributes to prelingual deafness, we searched for mutations in this gene in 65 affected Caucasian families originating from various countries, mainly Tunisia, France, New Zealand and the UK. Six of these families are consanguineous, and deafness was shown to be linked to the DFNB1 locus, 10 are small non consanguineous families in which the segregation of the trait has been found to be compatible with the involvement of DFNB1, and in the remaining 49 families no linkage analysis has been performed. A total of 62 mutant alleles in 39 families were identified. Therefore, mutations in Cx26 represent a major cause of recessively inherited prelingual deafness since according to the present results they would underlie approximately half of the cases. In addition, one specific mutation, 30delG, accounts for the majority (similar to 70%) of the Cx26 mutant alleles. It is therefore one of the most frequent disease mutations so far identified. Several lines of evidence indicate that the high prevalence of the 30delG mutation arises from a mutation hot spot rather than from a founder effect. Genetic counselling for prelingual deafness has been so far considerably impaired by the difficulty in distinguishing genetic and non genetic deafness in families presenting with a single deaf child. Based on the results presented here, the development of a simple molecular test could be designed which should be of considerable help.