Myotonia caused by mutations in the muscle chloride channel gene CLCN1
Myotonia caused by mutations in the muscle chloride channel gene CLCN1
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DOI：
10.1002/humu.10063
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发表时间：
2002-01-01
期刊：
影响因子：
3.9
通讯作者：
Pusch, M
中科院分区：
文献类型：
--
作者：
Pusch, M
人类纯粹的非综合征型、非营养不良性肌强直是由编码具有相似表型的骨骼肌钠通道 (SCN5A) 或骨骼肌氯通道 (CLCN1) 的基因突变引起的。氯离子通道肌强直可以是显性的（汤姆森型肌强直）或隐性的（贝克尔型肌强直）。 CLCN1 基因中已发现 60 多种导致肌强直的突变，其中只有少数是显性突变。显性突变的常见表型是突变型 WT 异二聚体中突变亚基的显性负效应，导致稳态开放概率电压依赖性向更正的、非生理性的电压发生很大转变。对引起疾病的突变特性的研究有助于了解 CLC-1 通道的功能特性，CLC-1 通道是氯离子通道九个成员基因家族的一部分。针对 CLC-1 获得的大量知识也可能有助于更好地了解其他 CLC 通道，其中三个通道也与遗传疾病有关。 Hum Mutat 19:423-434, 2002。(C) 2002 Wiley-Liss, Inc.
Pure non-syndromic, non-dystrophic myotonia in humans is caused by mutations in the genes coding for the skeletal muscle sodium channel (SCN5A) or the skeletal muscle chloride channel (CLCN1) with similar phenotypes. Chloride,channel myotonia can be dominant (Thomsen-type myotonia) or recessive (Becker-type myotonia). More than 60 myotonia-causing mutations in the CLCN1 gene have been identified, with only a few of them being dominant. A common phenotype of dominant mutations is a dominant negative effect of mutant subunits in mutant-WT heterodimers, causing a large shift of the steady-state open probability voltage-dependence towards more positive, unphysiological voltages. The study of the properties of disease causing mutations has helped in understanding the functional properties of the CLC-1 channel that is part of a nine,member gene family of chloride channels. The large body of knowledge obtained for CLC-1 may also help to better understand the other CLC channels, three of which are also involved in genetic diseases. Hum Mutat 19:423-434, 2002. (C) 2002 Wiley-Liss, Inc.