Loss of function mutations of the GJB2 gene detected in patients with DFNB1-associated hearing impairment

被引:51
作者
Palmada, M
Schmalisch, K
Böhmer, C
Schug, N
Pfister, M
Lang, F
Blin, N
机构
[1] Univ Tubingen, Inst Human Genet, Div Mol Genet, D-72074 Tubingen, Germany
[2] Univ Tubingen, Inst Physiol 1, D-72074 Tubingen, Germany
[3] Univ Tubingen, Dept Otolaryngol, D-72074 Tubingen, Germany
关键词
gap junction; connexins; Cx26; GJB2; mutations; Xenopus laevis; oocytes; functio; nal characterization;
D O I
10.1016/j.nbd.2005.10.005
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:112 / 118
页数:7
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