儿茶酚胺介导的多形性室速患者家系CASQ2基因F189L突变的基因分析  

A Novel mutation of F189L in CASQ2 in families with catecholaminergic polymorphic ventrictdar tachycardia

作　　者：刘茜蓓[1,2] Carlos Oberti 张贤钦[3,4] 柯铁[3,4] 张腾 Melvin Scheinman 胡大一[1] 王擎[3,4] 

机构地区：[1]北京大学人民医院心内科,100044 [2]北京大学深圳医院心内科 [3]Department of Molecular Cardiology,Center for Cardiovascular Genetics,Lemer Research Institute,The Cleveland Clinic,Cleveland,OH 44195,U.S.A [4]华中科技大学生命科学与技术学院人类基因组研究中心 [5]Electrophysiology Service,Section of Cardiology,Department of Medicine,University of California,San Francisco,CA 94143-1354,U.S.A

出　　处：《中华医学遗传学杂志》2008年第3期334-337,共4页Chinese Journal of Medical Genetics

基　　金：美国NIH R01 HL66251（Q.K.W）基金;国家重点基础研究发展计划资助“973”项目（2007CB512001和2007CB512002）;国家留学基金委中美联合培养博士项目（2006：3037）;美国心脏学会杰出研究员奖（0440157N）

摘　　要：目的在27例儿茶酚胺介导的多形性室速患者及家庭成员中寻找CASQ2基因突变。方法应用直接DNA序列分析对临床诊断为家族性多形性室速27例患者及家庭成员进行进行基因突变分析。应用Taqman基因分型检测在以1400名正常人群中确定CASQ2变异的频率。结果在一个多形性室速家系中发现了1个新的杂合子改变F189L。通过与多种生物比对，证实该改变发生于在第2结构域一个高度保守的氨基酸上，位于第5外显子的F189L的改变，使编码蛋白的第189位氨基酸由苯丙氨酸改变为亮氨酸。应用Taqman SNP genotyping assay分析方法证实正常人群1400名中未发现同样改变。在CASQ2基因中未发现其他引起疾病的基因突变。结论发现了CASQ2基因的1个新F189L突变。Objective To identify mutations and variants in CASQ2 gene in 27 CPVT patients/family members. Methods Mutational analysis was performed with direct DNA sequence analysis. The frequency of an identified CASQ2 variant was determined using the Taqman genotyping assay. Results A novel heterozygons mutation, F189L, in CASQ2 gene was identified in one family with CPVT. This mutation occurred at the evolutionarily, highly conserved phenylalanine residue at codon 189, and was not present in 1400 control individuals. No other disease-cansing mutations were identified in the CASQ2 gene. Conclusion A novel of F189L in the CASQ2 gene was identified.

关 键 词：心律失常 儿茶酚胺介导的多形性室速 CASQ2基因 

分 类 号：R733.72[医药卫生—肿瘤] R541.710.5[医药卫生—临床医学]