High frequency hearing loss correlated with mutations in the GJB2 gene
High frequency hearing loss correlated with mutations in the GJB2 gene
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DOI：
10.1007/s004390000273
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发表时间：
2000-04-01
期刊：
影响因子：
5.3
通讯作者：
Dahl, HHM
中科院分区：
文献类型：
--
作者：
Wilcox, SA;Saunders, K;Dahl, HHM
遗传性听力障碍影响大约1/2000的活产婴儿。编码皮毛连接蛋白26的基因GJB 2突变导致10%-20%的遗传性感音神经性听力损失。对106个至少有一名先天性耳聋患儿的家系进行了GJB 2基因突变分析和听力学检查。这些家庭是从医院的多学科诊所招募的，该诊所的功能是调查儿童感音神经性听力损失的病因，并为不同种族的人群提供服务。在74个家庭（80名儿童）中，病因与非综合征隐性愈合丧失一致。发现了6种不同的连接蛋白26突变，包括1种新突变。我们发现，GJB 2突变导致从轻度到重度听力障碍的一系列表型，高频范围（4000-8000 Hz）的发热损失是分子诊断为连接蛋白26听力障碍的儿童的特征。我们还证明，这种类型的听力学和高频听力损失是在一个类似规模的聋哑儿童组中发现的，其中一个突变只能被发现生病的连接蛋白26等位基因之一，这表明连接蛋白26参与在这些情况下的听力损失的病因。在我们对M34 T突变的研究中，只有复合杂合子表现出听力损失，提示常染色体隐性遗传。
Genetic hearing impairment affects approximately 1/2000 live births. Mutations in one gene, GJB2, coding fur connexin 26 cause 10%-20% of all genetic sensorineural hearing loss. Mutation analysis ill the GJB2 gene and audiology were performed on 106 families presenting with at least one child with congenital hearing loss. The families were recruited from a hospital-based multidisciplinary clinic, which functions to investigate the aetiology of sensorineural hearing loss in children and which serves an ethnically diverse population. In 74 families (80 children), the aetiology was consistent with non-syndromic recessive healing loss. Six different connexin 26 mutations, including one novel mutation, were identified. We show that GJB2 mutations cause a range of phenotypes from mild to profound hearing impairment and that loss of heating in the, high frequency range (4000-8000 Hz) is a characteristic feature in children with molecularly diagnosed connexin 26 hearing impairment. We also demonstrate that this type of audiology and high frequency hearing loss is found in a similar-sized group of deaf children in whom a mutation could only be found ill one of the connexin 26 alleles, suggesting connexin 26 involvement in the aetiology of hearing loss in these cases. In our study of the M34T mutation, only compound heterozygotes exhibited hearing loss, suggesting autosomal recessive inheritance.