QT延长综合征HERG基因新突变位点E505D的功能检测

目的 研究中国人QT延长综合征2型(LQT2)HERG基因突变(E505D)导致的功能改变。方法 将HERG基因野生型cRNA和突变型(E505D)cRNA分别和同时注射到非洲爪蟾卵母细胞,采用双电极电压钳技术记录非洲爪蟾卵母细胞膜上电流的表达,了解基因突变对电流的影响。结果 单独注射突变型cRNA记录到的电流与注射双蒸水记录到的电流差异无显著性。野生型和突变型cRNA共同注射记录到的电流显著低于单独注射野生型cRNA,电流改变呈负电位占优势的方式。结论 HERG基因突变使快速激活延迟整流性钾通道电流减小,心室复极时间延长,QTc延长,证实HERG基因突变与LQT2相关。

Function of HERG new mutation E505D in LQT2

Objective To study the function of HERG mutation ( E505D) in LQT2 in China. Methods Xenopus oocytes were injected with wild HERG cRNA, mutant HERG cRNA(E505D) or wild HERG cRNA combined with mutant HERG cRNA(E505D). Current expression was recorded with double electrode voltage clamp. Results The currents recorded on the oocytes with mutant HERG cRNA(E505D) was similar to those with double distilled water. The currents recorded on the oocytes coinjected with wild HERG cRNA and mutant HERG cRNA(E505D) was lower than those injected with wild HERG cRNA. Mutation caused dominant negative suppression of HERG function. Conclusions HERG mutation could decrease the delayed rectifying K current, delay ventricular repolarization and prolong QTc. HERG mutation could correlate with LQT2.