短QT间期并Brugada样心电图患者SCN5A突变的分子遗传学及电生理机制  

Molecular genetic and electrophysiology mechanism of patient with concomitant Brugada-like and short QT electrocardiogram

作　　者：周慧[1] 俞建华[1] 胡金柱[1] 程晓曙[1] 洪葵[1] 

机构地区：[1]南昌大学第二附属医院心血管内科,330006

出　　处：《中华心律失常学杂志》2013年第1期22-25,共4页Chinese Journal of Cardiac Arrhythmias

摘　　要：目的发现1例短QT间期合并Brugada样心电图患者，具有猝死家族史，报道其分子遗传及电生理机制研究结果。方法通过DNA直接测序法进行候选基因突变筛查。对表达突变基因序列的HEK293细胞进行膜片钳分析，研究其生物学特性。结果基因筛查发现患者SCN5A基因第2066位核苷酸G〉A杂合子错义突变，从而导致第689位密码子由精氨酸变成组氨酸（R689H）。细胞膜片钳分析发现R689H突变型钠通道不能产生任何电流，提示R689H突变功能丧失。结论首次发现SCN5A基因R689H杂合子错义突变导致蛋白功能丧失，以及短QT问期合并Brugada样心电图的重叠表型。Objective To investigate the molecular genetic and electrophysiology mechanism of a pa- tient with the family history of sudden death showed Brugada-like and short QT interval electrocardiogram （ECG）. Methods The candidate genes were screening by direct sequencing. Whole cell patch clamp analysis of HEK293 cells expressing a mutant channel with the patient＇ s sequence was used to investigate the biophysi- cal properties of the channel. Results Sequence analysis of the coding region of the SCN5A gene,identified a G to A heterozygous missense mutation at nucleotide site 2066 that resulted in an amino acid substitution of ar- ginine to histidine at amino acid site 689 （R689H）. Patch clamp analysis showed that the R689H failed to gen- erate current when heterologously expressed in HEK293 cells, indicating it was a loss-of-function mutation. Conclusion Our finding firstly showed that a heterozygous missense mutation R689H in SCNSA results in a loss of protein function and the co-existents of the Brugada-like and short QT interval ECG phenotypes.

关 键 词：短QT间期 BRUGADA 突变 SCN5A基因 

分 类 号：R541.7[医药卫生—心血管疾病]