Loss of function mutations of the GJB2 gene detected in patients with DFNB1-associated hearing impairment
Loss of function mutations of the GJB2 gene detected in patients with DFNB1-associated hearing impairment
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DOI：
10.1016/j.nbd.2005.10.005
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发表时间：
2006-04-01
影响因子：
6.1
通讯作者：
Blin, N
中科院分区：
文献类型：
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作者：
Palmada, M;Schmalisch, K;Blin, N
编码差距连接蛋白连接蛋白26（Cx26）的GJB 2突变是遗传性和散发性非综合征性听力损伤的主要原因之一。本研究旨在从功能上表征非综合征性听力障碍患者中更常见的GJB2突变。在非洲爪蟾卵母细胞中注射野生型和突变的cRNA后，通过非偶联卵母细胞中的去极化激活电导来测量Cx26半通道活性。所有突变体显示部分或完全缺陷的表型，除了V（27 I）Cx26，多态性作为阳性对照进行测试。以等摩尔水平注射的野生型和突变型Cx 26的共表达揭示了p.M34T、p.V371和p.182M而不是p.G59V、p.L90P、p.R127H和p.R143W发挥显性抑制作用。当与Cx30共表达时，Cx26在耳蜗中部分共定位的连接蛋白，所有突变体具有显性行为。本研究为提高听力障碍患者的遗传诊断和咨询提供了重要的数据。(c)2005年爱思唯尔公司所有权利已收到。
Mutations in GJB2, which encodes the gap junction protein connexin 26 (Cx26), are one of the major causes for inherited and sporadic nonsyndromic hearing impairment. This study aimed to functionally characterize more frequent GJB2 mutations identified in patients showing nonsyndromic hearing impairment. Following injection of wild type and mutated cRNA in Xenopus oocytes, Cx26 hemichannel activity was measured by depolarization activated conductance in noncoupled oocytes. All mutants showed a partially or completely defective phenotype, except V(27I)Cx26, a polymorphism tested as positive control. Coexpression of wild type and mutant Cx26 injected at equimolar levels revealed that p.M34T, p.V371 and p.182M, but not p.G59V, p.L90P, p.R127H and p.R143W exert a dominant inhibitory effect. When coexpressed with Cx30, a connexin partially colocalized with Cx26 in the cochlea, all mutants had a dominant behavior. This study provides data that might be important for the improvement of genetic diagnosis and counseling for patients with hearing impairment. (c) 2005 Elsevier Inc. All rights received.