Novel mutation in the SCN5A gene associated with arrhythmic storm development during acute myocardial infarction
Novel mutation in the SCN5A gene associated with arrhythmic storm development during acute myocardial infarction
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DOI：
10.1016/j.hrthm.2007.03.040
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发表时间：
2007-08-01
期刊：
影响因子：
5.5
通讯作者：
Antzelevitch, Chares
中科院分区：
文献类型：
--
作者：
Hu, Dan;Viskin, Sami;Antzelevitch, Chares
Brugada综合征（一种与SCN 5A突变相关的遗传性疾病）并发的室性心动过速（VT）和室颤（VF）以及急性心肌梗死（AMI）并发的VF均与2期折返有关。本研究的目的是检查SCN 5A突变对VT/VT的贡献。AMI并发室颤：方法19例AMI期间发生室颤的连续患者入选本研究。野生型和突变型SCN 5A基因与SCN 1B在TSA 201细胞中共表达，并采用全细胞膜片钳技术进行研究。在同一等位基因上检测到H558 R多态性。与其他18名患者不同，他们每个人在AMI期间发生1-2次VF发作，突变携带者在最初的12小时内发生了6次VT/VF发作。ALL VT/VF发作与ST段改变相关，并由短偶联性期外收缩引发。为发现Brugada和长QT综合征而进行的氟卡尼和腺苷激发试验均为阴性。G400 A和G400 A + H558 R在-35 mV时的峰值电流分别比WT低70.7%和88.4%（P
BACKGROUND Ventricular tachycardia (VT) and ventricular fibrillation (VF) complicating Brugada syndrome, a genetic disorder Linked to SCN5A mutations, and VF complicating acute myocardial infarction (AMI) both have been linked to phase 2 reentry.OBJECTIVE Given the mechanistic similarities in arrhythmogenesis, the purpose of this study was to examine the contribution of SCN5A mutations to VT/VF complicating AMI.METHODS Nineteen consecutive patients developing VF during AMI were enrolled in the study. Wild-type (WT) and mutant SCN5A genes were coexpressed with SCN1B in TSA201 cells and studied using whole-cell patch clamp techniques.RESULTS Among the cohort of 19 patients, one missense mutation (G400A) in SCN5A was detected in a conserved region. An H558R polymorphism was detected on the same allele. Unlike the other 18 patients, who each developed 1-2 VF episodes during AMI, the mutation carrier developed six episodes of VT/VF within the first 12 hours. ALL VT/VF episodes were associated with ST-segment changesand were initiated by short-coupled extrasystoles. Flecainide and adenosine challenge performed to unmask Brugada and long QT syndromes both were negative. Peak G400A and G400A+H558R current were 70.7% and 88.4% Less than WT current at -35 mV (P