首页> 外文期刊>Human mutation >Analysis of the human KCNH2(HERG) gene: identification and characterization of a novel mutation Y667X associated with long QT syndrome and a non-pathological 9 bp insertion.
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Analysis of the human KCNH2(HERG) gene: identification and characterization of a novel mutation Y667X associated with long QT syndrome and a non-pathological 9 bp insertion.

机译:人类KCNH2(HERG)基因分析:鉴定和表征与长QT综合征和非病理性9 bp插入相关的新型突变Y667X。

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摘要

Long QT (LQT) syndrome is a potentially life-threatening disorder, characterized by a distinct cardiac arrhythmia known as torsades de pointes. Mutations within a number of genes linked to the familial form, including that coding for a cardiac potassium channel called KCNH2 (HERG), have been described based on the characterized genomic organization. A standardized method was developed to screen the entire gene for gene variants. We report a single base pair substitution, introducing a premature STOP codon at codon 667 of the gene in a healthy individual with an extended QTc interval (460 msec). In vitro expression of the codon Y667X variant in Xenopus oocyte suggests that the autosomal dominant variant does not function in a dominantegative manner and cannot co-assemble to form a channel, resulting in a reduction of the KCNH2 current, and an extension of the QT interval. This indicates that pathogenic LQT gene variants exist in the apparently normal population, the prognosis and clinical consequences of which remain to be determined. The assays described should facilitate future studies into this area. Copyright 2000 Wiley-Liss, Inc.
机译:长QT(LQT)综合征是一种潜在的威胁生命的疾病,其特征是明显的心律不齐,称为尖端扭转型室速。基于特征基因组组织,已经描述了与家族形式相关的许多基因中的突变,包括编码称为钾钾通道(KCNH2(HERG)的心脏钾通道)的基因。开发了一种标准化方法来筛选整个基因的基因变异。我们报告了一个单碱基对取代,在健康个体中以延长的QTc间隔(460毫秒)在该基因的667号密码子处引入了一个过早的STOP密码子。 Xenopus卵母细胞中密码子Y667X变体的体外表达表明常染色体显性变体不能以显性/负性方式起作用,并且不能共同装配形成通道,从而导致KCNH2电流的减少和核糖体的延伸。 QT间隔。这表明病原性LQT基因变异存在于显然正常的人群中,其预后和临床后果尚待确定。所描述的测定方法应有助于将来对该领域的研究。版权所有2000 Wiley-Liss,Inc.

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