中国儿茶酚胺敏感性多形性室性心动过速患者RyR2基因突变分析

The mutation analysis of RyR2 gene in Chinese patients with catecholaminergic polymorphic ventricular tachycardia

目的拟研究中国儿茶酚胺敏感性多形性室性心动过速(CPVT)患者的兰尼丁受体(RyR2)基因变异情况。方法研究对象来自参与中国离子通道病全国注册的4个CPVT家系,收集其基本临床资料。提取先证者及其父母DNA样本,用PCR方法扩增RyR2基因突变集中的45个外显子及内含子-外显子拼接部位序列并直接测序。结果发现2个CPVT先证者分别携带杂合突变p.Arg169Gln和p.Leu2534Val。在其父母和100名正常对照者中未发现相同突变,提示这两个突变均为新发突变(de novo),并在多个物种中高度保守。结论结合已知突变报道推测p.Arg169Gln可能是引起亚洲人CPVT的热点突变位点。

Objective To investigate RyR2 mutations in the Chinese patients with catecholaminergic polymorphic ven- tricular tachycardia （CPVT）. Methods Four CPVT families provided by the National Channellopathy Registry Study were selected. DNA samples of the probands and their parents were extracted from serum leukocyte. 45 exons where the known mutation clusters located were first identified by direct DNA-sequencing. Results Two different heterozygous mu- tations p. Arg169Gln and p. Leu2534Val were identified to cause amino acid missense mutation in two unrelated CPVT ca- ses, and they were absent in the parents and 100 unrelated control subjects. All of mutated residues exhibit high conserva- tion across species. Conclusion Combined with known reports, p. Arg169Gln might be a mutation hotspot in Asian CPVT patients.