心电图不典型的Brugada综合征家系调查及初步分子遗传学研究

Brugada syndrome without typical electrocardiogram:clinical report,family investigation and preliminary molecular genetic studies

目的 在 1个Brugada综合征病人发现特殊的心电图表现 :胸前导联ST段呈上斜形抬高 ,凸面向上 ,无明显J波 ,无右束支阻滞 (RBBB)。对其家系进行了临床调查及SCN5A基因 (编码心脏电压门控Na+ 通道蛋白α亚单位基因 )突变检测 ,分析其临床及分子遗传学特征。方法 家系临床调查包括收集所有 15个家系成员的病史资料及进行常规体格检查 ,12导联心电图、超声心动图、X光胸片检查等。采用PCR 单链构象多态性技术 (SSCP)结合DNA序列测定证实 ,对病人SCN5A的全部 2 8个外显子进行突变检测。结果 所有成员均无器质性心脏病的证据 ,先证者有晕厥病史 ,并被记录到频发极短配对间期的室性早搏、多形室性心动过速及心室颤动 ,而其他家族成员均无晕厥或猝死病史 ,先证者的 1个儿子及侄儿与其静息心电图表现相似。基因突变检测未能在病人的SCN5A基殷中发现遗传缺陷。结论 发现了一种特殊的Brugada心电图模式 ,对目前Brugada综合征诊断标准提出质疑 ,并提示存在遗传不均一性 ,SCN5A可能不是惟一的致病基因。

Objective A case of ventricular tachycardia/fibrillation(VT/VF) with an electrocardiogram (ECG) pattern of upward convexity shaped ST segment elevation without prominent J wave in right precodial leads was reported.To elucidate the character of this type of Brugada syndrome by further clinical investigation of his family members and mutation screening of SCN5A,the gene encoding cardiac sodium channel protein α unit.Method Clinical data including medical history,physical examination,ECG,echocardiogram,chest X-ray were collected from totally 15 members of the family.PCR and single strand conformation polymorphism analysis (SSCP) were combined with DNA sequencing confirmation to screen all 28 exons of SCN5A gene.Result Episodes of repeated syncope,aborted sudden death,ECG frequent runs of very closely coupled extrasystols and VT/VF were recorded in the proband,but not in his family member.None of the family members had evidence of structural heart defect.However,similar ECG findings of ST segment elevation were seen in one patient's son (age 14) and one nephew (age 13).No genetic defect was identified in the exons of SCN5A gene on the proband.Conclusion A novel ECG pattern of Brugada syndrome has been identified,which is a challenge to current diagnosis criteria. No genetic defect is revealed, which might serve as an evidence of genetic heterogeneity.SCN5A may be not the only gene responsible for Brugada syndrome.