Frequency and distribution of GJB2 (connexin 26) and GJB6 (connexin 30) mutations in a large North American repository of deaf probands
Frequency and distribution of GJB2 (connexin 26) and GJB6 (connexin 30) mutations in a large North American repository of deaf probands
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DOI：
10.1097/01.gim.0000078026.01140.68
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发表时间：
2003-07-01
影响因子：
8.8
通讯作者：
Nance, WE
中科院分区：
文献类型：
--
作者：
Pandya, A;Arnos, KS;Nance, WE
目的：重度听力损失的发生率为千分之一，其中一半是遗传病因。在过去的十年中，在确定综合征和非综合征性耳聋的发病机制方面取得了快速进展。迄今为止最重要的临床发现是发现GJB2在DFNB1位点的突变是许多国家重度语前耳聋的主要原因。最近，当GJB6基因缺失时，GJB2突变被证明会导致耳聋。我们报告了GJB2和GJB6突变在北美大型聋人先证者DNA库中的流行情况，并记录了家族种族和亲代交配类型对人群中这些突变频率的深远影响。方法：通过加劳德特大学研究所进行的《聋人及重听儿童和青少年年度调查》确定聋人先证者。在获得知情同意后收集教育、病因学和听力学信息。采用测序和PCR方法对GJB2和GJB6基因座进行DNA研究。结果：GJB2突变占整个样本中耳聋的22.2%，但在亚洲人、非洲裔美国人和西班牙裔美国人中、聋人与聋人、聋人与听力配对的先证者以及听力父母单纯性和多重兄弟姐妹的先证者中差异显著。在我们的样本中，GJB2/GJB6耳聋的总发病率为2.57%。结论：GJB2突变在美国耳聋中占很大比例，某些突变具有较高的种族偏好。GJB2位点杂合子应筛选GJB6缺失作为耳聋的原因。GJB2和GJB6的分子检测应提供给所有非综合征性听力损失患者。
Purpose: Profound hearing loss occurs with a frequency of 1 in 1000 live births, half of which is genetic in etiology. The past decade has witnessed rapid advances in determining the pathogenesis of both syndromic and nonsyndromic deafness. The most significant clinical finding to date has been the discovery that mutations of GJB2 at the DFNB1 locus are the major cause of profound prelingual deafness in many countries. More recently, GJB2 mutations have been shown to cause deafness when present with a deletion of the GJB6 gene. We report on the prevalence of GJB2 and GJB6 mutations in a large North American Repository of DNA from deaf probands and document the profound effects of familial ethnicity and parental mating types on the frequency of these mutations in the population. Methods: Deaf probands were ascertained through the Annual Survey of Deaf and Hard of Hearing Children and Youth, conducted at the Research Institute of Gallaudet University. Educational, etiologic, and audiologic information was collected after obtaining informed consent. DNA studies were performed for the GJB2 and GJB6 loci by sequencing and PCR methods. Results: GJB2 mutations accounted for 22.2% of deafness in the overall sample but differed significantly among Asians, African-Americans and Hispanics and for probands from deaf by deaf and deaf by hearing matings, as well as probands from simplex and multiplex sibships of hearing parents. In our sample, the overall incidence of GJB2/GJB6 deafness was 2.57%. Conclusion: GJB2 mutations account for a large proportion of deafness in the US, with certain mutations having a high ethnic predilection. Heterozygotes at the GJB2 locus should be screened for the GJB6 deletion as a cause of deafness. Molecular testing for GJB2 and GJB6 should be offered to all patients with nonsyndromic hearing loss.