钠通道相关遗传性心律失常的SCN5A基因筛查  

Gene screening of SCN5A in patients with Na^+ channel related inherited arrhythmias

作　　者：高元丰[1] 刘文玲[1] 胡大一[1] 梁璐[2] 李小梅[3] 周金台[4] 郭成军[5] 袁越[6] 李蕾[1] 李翠兰[1] 

机构地区：[1]北京大学人民医院心脏中心,北京100044 [2]首都儿科研究所 [3]清华大学华信医院心脏中心 [4]天津医科大学总医院心内科 [5]首都医科大学附属北京安贞医院心内科 [6]北京儿童医院

出　　处：《中国心脏起搏与心电生理杂志》2013年第2期107-110,共4页Chinese Journal of Cardiac Pacing and Electrophysiology

基　　金：国家自然基金(项目编号:81170089);教育部博士点基金(项目编号:20110001110046)

摘　　要：目的研究编码钠通道的基因SCN5A基因变异在国人遗传性心律失常患者中的分布特征。方法基于临床症状及心电图表现诊断为3型长QT综合征(LQTS)患者7例、房室传导阻滞(AVB)7例、病窦综合征(SSS)2例以及早期复极综合征(ERS)1例,共17例患者为研究对象,利用聚合酶链式反应和直接测序法对所有患者的DNA样本进行SCN5A基因筛查,对结果阳性者再进行家系中其他成员的筛查。结果 17例患者中,在1例LQT3表型的患者身上发现一个SCN5A基因突变c.4418 T>C(p.Phe1473Ser),该突变位于SCN5A的第25个外显子上,父母血液标本DNA未见相应突变;在另外3例LQTS患者身上发现4个单核苷酸多肽性(SNPs),分别为c.1141-3C>A、c.1339-24G>A、c.1673A>G(p.His 558 Arg)、c.3269 C>T(p.Pro 1090Leu)。在3例AVB表型患者身上发现3个SNPs,分别为c.1339-24G>A、c.1673A>G(p.His 558 Arg)、c.3578G>A(p.Arg1193 Gln)。在1例SSS患者身上发现一个SNP c.3269 C>T(p.Pro 1090Leu)。在1例ERS患者身上未发现任何变异。结论在17例钠通道相关遗传性心律失常患者中发现了SCN5A基因上一个新发突变以及5个SNPs;该突变所在氨基酸位点Phe1473极有可能是一个容易发生新发突变的热点位置。Objective To investigate the distribution of SCNSA variations in chinese patients with Na~ channel related in- herited arrhythmias. Methods Totally, 17 patients with clinical and Electrocardiographic （ECG） features of long-QT syn- drome（LQTS）, atrioventricular-block （AVB）, sinus sick syndrome （SSS）, early repolarization syndrome （ERS） were enrolled as candidates. DNA samples were collected from their peripheral blood cells. Polymerase chain reaction and direct sequencing were done subsequently to screen the patients of any possible SCNSA variations. In addition, family members of patients with positive result were also screened. Results A missense mutation, located on exon 25 of SCNSA, c. 4418 T〉C （p. Phe1473Ser） was detected on a LQTS patient, no such variation was found on the patient＇s parents. Four SNPs were found on the other three LQTS patients, which are c. 1141-3C〉A, c. 1339-24G〉A, c. 1673A〉G （p. His 558 Arg）, c. 3269 C〉T （p. Pro 1090Leu）. There were another three SNPs detected on three AVB patients： c. 1339-24G〉A, c. 1673A〉G （p. His 558 Arg）, c. 3578G〉A （p. Argl193 Gin）. In addition, c. 3269 C〉T （p. Prol09OLeu） was also detected on a SSS patient while no variationwas found on the ERS patient. Condution One de novo mutation and five SNPs exist on patients with Na~ channel re- lated inherited arrhythmias. In addition, the amino-acid site Phe1473, in which the mutation locates, might be a de novo mutation hot spot.

关 键 词：心血管病学 SCN5A基因 长QT综合征 房室传导阻滞 早期复极综合征 病窦综合征 单核苷酸多态性 

分 类 号：R541.7[医药卫生—心血管疾病] R541.74[医药卫生—内科学]