Connexin-26 mutations in sporadic and inherited sensorineural deafness
Connexin-26 mutations in sporadic and inherited sensorineural deafness
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DOI：
10.1016/s0140-6736(97)11124-2
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发表时间：
1998-02-07
期刊：
影响因子：
168.9
通讯作者：
Gasparini, P
中科院分区：
文献类型：
--
作者：
Estivill, X;Fortina, P;Gasparini, P
背景 听力障碍影响千分之一的婴儿和 4% 的 45 岁以下人群。先天性耳聋是遗传性的或明显散发性的。我们之前已经证明，13 号染色体上的 DFNB1 是约 80% 地中海家庭中隐性耳聋的主要位点，并且连接蛋白 26 基因间隙连接蛋白 β 2 (GJB2) 在 DFNB1 家族中发生突变。我们研究了家族性和散发性耳聋病例中 GJB2 基因的突变。方法我们从 82 个家庭获取了 DNA 样本 来自意大利和西班牙的患有隐性非综合征性耳聋的受试者以及 54 名患有明显散发性先天性耳聋的无关参与者。我们分析了 GJB2 基因编码区的突变。我们还对来自意大利和西班牙普通人群的 280 名无关人员进行了移码突变 35delG 检测。结果显示，49% 的隐性耳聋参与者和 37% 的散发病例存在 GJB2 基因突变； 35delG突变占GJB2突变的85％，其他6种突变占等位基因的6％，在9％的DFNB1等位基因中未检测到GJB2编码区的变化。一般人群中35delG突变的携带频率为31分之一（95％CI为19分之一到87分之一）。解释GJB2基因突变 是遗传性和明显散发性先天性耳聋的主要原因。突变 35delG 是感音神经性耳聋最常见的突变。鉴定 GJB2 基因中的 35delG 和其他突变应该有助于对最常见遗传性耳聋的诊断和咨询。
Background Hearing impairment affects one infant in 1000 and 4% of people aged younger than 45 years. Congenital deafness is inherited or apparently sporadic. We have shown previously that DFNB1 on chromosome 13 is a major locus for recessive deafness in about 80% of Mediterranean families and that the connexin-26 gene gap junction protein beta 2 (GJB2) is mutated in DFNB1 families, We investigated mutations in the GJB2 gene in familial and sporadic cases of deafness.Methods We obtained DNA samples from 82 families from Italy and Spain with recessive non-syndromic deafness and from 54 unrelated participants with apparently sporadic congenital deafness. We analysed the coding region of the GJB2 gene for mutations. We also tested 280 unrelated people from the general populations of Italy and Spain for the frameshift mutation 35delG.Findings 49% of participants with recessive deafness and 37% of sporadic cases had mutations in the GJB2 gene; The 35delG mutation accounted for 85% of GJB2 mutations, six other mutations accounted for 6% of alleles, and no changes in the coding region of GJB2 were detected in 9% of DFNB1 alleles., The carrier frequency of mutation 35delG among people from the general population was one in 31 (95% CI one in 19 to one in 87).Interpretation Mutations in the GJB2 gene are a major cause of inherited and apparently sporadic congenital deafness. Mutation 35delG is the most common mutation for sensorineural deafness. Identification of 35delG and other mutations in the GJB2 gene should facilitate diagnosis and counselling for the most common genetic form of deafness.