HERG基因新突变与家族性QT延长综合征  

Novel HERG gene mutation and congenital long QT syndrome

作　　者：董颖雪[1] 杨延宗[1] 林治湖[1] 滕思勇[2] 林春霞[2] 马丽娟[2] 刘金秋[1] 李世军[1] 惠汝太 

机构地区：[1]大连医科大学附属第一医院心内科,116011 [2]中国医学科学院中国协和医科大学阜外心血管病医院中德实验室

出　　处：《中华心血管病杂志》2002年第4期202-205,共4页Chinese Journal of Cardiology

摘　　要：目的　对一祖孙四代的QT延长综合征 (LQTS)家系进行临床研究及分子遗传学分析 ,并揭示该家系成员基因型与基因表型之间的关系。方法　搜集整理先证者及该家系成员的临床资料 ,采用PCR SSCP进行基因突变位点的初步检测 ,并应用直接测序的方法进行验证。结果　该家系2 6例中达到临床诊断标准者 6例 ,可疑诊断 1例。其共同的心电图特征为 :QTc≥ 0 46s,T波宽大双峰 ,U波明显。基因检测结果表明 ,7例成员HERG基因的 10号外显子均出现一个新的单碱基的转换突变 (CGA2 5 87TGA) ,该无义突变导致快速激活延迟整流性钾通道 (IKr) ,缺失了 2 96个氨基酸。结论　该研究发现了LQTS一个新的致病基因突变位点 ,并验证了LQTS 2型患者的心电图特点。推测该家系中致病基因携带者心电图U波的出现可能同IKr蛋白质C末端的缺失有关。Objective To carry out clinical and molecular genetic analyses in a big kindred including four generations with long QT syndrome (LQTS) and to explore the genotype-phenotype interrelationships between kindred members. Methods All medical records of the proband and family members were collected. Preliminary analysis on mutation was done by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), followed by direct sequencing for confirmation. Results Of the 26 members 6 were diagnosed clinically as LQTS and one was not ascertained. The common ECG characteristics were: QTc≥0.46 s, broad and notched T wave and obvious U wave. A novel mutation, which is a single base change (CGA2587TGA), was found in No. 10 exon of HERG gene. This nonsense mutation induces the deletion of 296 amino acids in the rapid activating component of delayed rectifier potassium channel ( I _ Kr ). Conclusions This study reveals a new LQTS-related gene mutation and the ECG characteristics of patients with LQTS type 2. It is suggested that the appearance of U wave in new gene carriers may be related to the deletion of C-terminal of the I _ Kr protein.

关 键 词：QT延长综合征 HERG基因 基因突变 心律失常 

分 类 号：R541.7[医药卫生—心血管疾病] R540.41[医药卫生—内科学]