Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1
Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1
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DOI：
10.1006/geno.1998.5361
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发表时间：
1998-07-01
期刊：
影响因子：
4.4
通讯作者：
Keating, MT
中科院分区：
文献类型：
--
作者：
Splawski, I;Shen, JX;Keating, MT
长QT综合征（LQT）是一种引起晕厥和心律失常猝死的心脏疾病。LQT的特点是心电图上QT间期延长，是心脏复极异常的指示。编码心脏离子通道的基因KVLQT1、HERG、SCN5A和KCNE1的突变可导致LQT。在这里，我们定义了三个LQT基因的完整基因组结构，并利用这些信息来识别疾病相关的突变。KVLQT1由16个外显子组成，全长约400kb。HERG由16个外显子组成，全长55 kb。KCNE1由三个外显子组成。这些基因的每个内含子分别在供体剪接位点和受体剪接位点上含有不变的GT和AG。内含子序列用于设计引物对扩增所有外显子。受KVLQT1、HERG和KCNE1突变影响的家族性和散发性病例现在可以进行遗传筛选，以确定有患这种疾病风险的个体。这项工作对症状前诊断和治疗具有临床意义。(C) 1998学术出版社。
Long QT syndrome (LQT) is a cardiac disorder causing syncope and sudden death from arrhythmias. LQT is characterized by prolongation of the QT interval on electrocardiogram, an indication of abnormal cardiac repolarization. Mutations in KVLQT1, HERG, SCN5A, and KCNE1, genes encoding cardiac ion channels, cause LQT. Here, we define the complete genomic structure of three LQT genes and use this information to identify disease-associated mutations. KVLQT1 is composed of 16 exons and encompasses approximately 400 kb. HERG consists of 16 exons and spans 55 kb. Three exons make up KCNE1. Each intron of these genes contains the invariant GT and AG at the donor and acceptor splice sites, respectively. Intron sequences were used to design primer pairs for the amplification of all exons. Familial and sporadic cases affected by mutations in KVLQT1, HERG, and KCNE1 can now be genetically screened to identify individuals at risk of developing this disorder. This work has clinical implications for presymptomatic diagnosis and therapy. (C) 1998 Academic Press.