Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-Segment elevation, short QT intervals, and sudden cardiac death
Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-Segment elevation, short QT intervals, and sudden cardiac death
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DOI：
10.1161/circulationaha.106.668392
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发表时间：
2007-01-30
期刊：
影响因子：
37.8
通讯作者：
Wolpert, Christian
中科院分区：
文献类型：
--
作者：
Antzelevitch, Charles;Pollevick, Guido D.;Wolpert, Christian
背景-心脏离子通道病是家族性心律失常综合征数量和多样性不断增加的原因.我们描述了一个新的临床实体，包括ST段抬高的右胸导联心电图，短于正常QT间期，和心脏性猝死的历史。方法和结果-82个连续的先证者Brugada综合征进行了筛选离子通道基因突变与直接测序。进行定点诱变，并用编码野生型或突变型CACNB 2b（Ca-v β 2b）、CACNA 2D 1（Cav（α 2 δ 1））和用增强型黄色荧光蛋白（Ca（v）1.2）标记的CACNA 1C的cDNA共转染CHO-K1细胞。在48至72小时后进行全细胞膜片钳研究。3例先证者显示ST段抬高和校正的QT间期
Background - Cardiac ion channelopathies are responsible for an ever- increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST- segment elevation in the right precordial ECG leads, a shorter- than- normal QT interval, and a history of sudden cardiac death.Methods and Results - Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing. Site-directed mutagenesis was performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b ( Ca-v beta 2b), CACNA2D1 ( Cav(alpha 2 delta 1)), and CACNA1C tagged with enhanced yellow fluorescent protein ( Ca(v)1.2). Whole- cell patch- clamp studies were performed after 48 to 72 hours. Three probands displaying ST- segment elevation and corrected QT intervals