A deletion involving the connexin 30 gene in nonsyndromic hearing impairment.
A deletion involving the connexin 30 gene in nonsyndromic hearing impairment.
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DOI：
10.1056/nejmoa012052
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发表时间：
2002-01-24
影响因子：
158.5
通讯作者：
Moreno, F
中科院分区：
文献类型：
--
作者：
del Castillo, I;Villamar, M;Moreno, F
背景：遗传性听力障碍在每2000名新生儿中约影响1人。在不同人群中，多达50%的常染色体隐性非综合征型语前聋患者在13q12位点的DFNB1处编码间隙连接蛋白连接蛋白26（GJB2）的基因存在突变。然而，很大一部分（10% - 42%）具有GJB2突变的患者只有一个突变等位基因；伴随的突变尚未被确定。也有报道在GJB2无突变的与DFNB1相关的家族病例。
方法：我们评估了33名无关的仅有一个GJB2突变等位基因的非综合征型语前聋先证者。9名受试者有与DFNB1连锁的证据。我们利用13q12上标记的单倍型分析来寻找除涉及GJB2之外的突变。
结果：我们在编码连接蛋白30（GJB6）的基因中鉴定出一个342kb的缺失，据报道该蛋白与内耳中的连接蛋白26一起表达。该缺失向远端延伸至GJB2，但GJB2保持完整。分离并测定了缺失的断点连接序列，并针对这种常见突变开发了一种特异性诊断测试。33名受试者中有22名对于GJB6和GJB2突变均为杂合子，包括所有9名有与DFNB1连锁证据的受试者。2名受试者对于GJB6突变是纯合子。
结论：GJB6中一个342kb的缺失是导致西班牙人群语前聋的第二常见突变。我们的数据表明，包含两个基因（GJB2和GJB6）的复杂位点DFNB1的突变可导致语前聋的单基因或双基因遗传模式。（《新英格兰医学杂志》2002年；346:243 - 249）版权所有（C）2002马萨诸塞州医学协会
Background: Inherited hearing impairment affects about 1 in 2000 newborns. Up to 50 percent of all patients with autosomal recessive nonsyndromic prelingual deafness in different populations have mutations in the gene encoding the gap-junction protein connexin 26 (GJB2) at locus DFNB1 on chromosome 13q12. However, a large fraction (10 to 42 percent) of patients with GJB2 mutations have only one mutant allele; the accompanying mutation has not been identified. DFNB1-linked familial cases with no mutation in GJB2 have also been reported.Methods: We evaluated 33 unrelated probands with nonsyndromic prelingual deafness who had only one GJB2 mutant allele. Nine subjects had evidence of linkage to DFNB1. We used haplotype analysis for markers on 13q12 to search for mutations other than the one involving GJB2.Results: We identified a 342-kb deletion in the gene encoding connexin 30 (GJB6), a protein that is reported to be expressed with connexin 26 in the inner ear. The deletion extended distally to GJB2, which remained intact. The break-point junction of the deletion was isolated and sequenced, and a specific diagnostic test was developed for this common mutation. Twenty-two of the 33 subjects were heterozygous for both the GJB6 and GJB2 mutations, including all 9 with evidence of linkage to DFNB1. Two subjects were homozygous for the GJB6 mutation.Conclusions: A 342-kb deletion in GJB6 is the second most frequent mutation causing prelingual deafness in the Spanish population. Our data suggest that mutations in the complex locus DFNB1, which contains two genes (GJB2 and GJB6), can result in a monogenic or a digenic pattern of inheritance of prelingual deafness. (N Engl J Med 2002;346:243-9.) Copyright (C) 2002 Massachusetts Medical Society.