心房静止一家系调查及致病基因研究

One familial atrial standstill and its genetics study

目的探讨家族性心房静止可能的发病机制及致病基因。方法通过分析一家族性心房静止患者的临床、心电生理表现,探讨其可能的发病机制;候选基因法寻找其可能致病基因。结果此家系含有44名成员,其中有5例患者,可能为常染色体不完全显性遗传。5例患者均表现为20多岁开始出现心动过缓,随着年龄的增加逐渐表现为心房扑动、心房颤动、房室传导阻滞,最终发展成为心房静止。此次检查心电图均表现为P波消失、心动过缓、房室传导阻滞等,多谱勒超声在跨二尖瓣与跨三尖瓣水平均未见A峰,心房电生理检查亦不能诱发心房激动,其中3例已安装起搏器。根据文献报道进一步筛查了SCN5A及connexin 40的所有外显子及启动子区序列,未发现错义突变。结论该家系可明确诊断为心房静止;其发病原因可能是常染色体不完全显性遗传;此家系心房静止可能由其它一个或多个新的基因突变引起。

Objective To discuss the potential mechanism and virulence gene for familial artial standstill. Methods To investigate the clinical manifestation and electrophysiological characteristics of one familial patient with artial standstill （AS）, and search for the possible virulence gene by candidate gene approach method. Results Forty-four family members were clinically evaluated, five of them were unambiguously affected by AS. Their clinical histories were very similar, first presented with symptoms of syncope in their early twenties and symptoms worsened with age. Before total AS, atrial bradycardia, atrial fibrillation, atrioventricular block could be found as ECG record. In this investigation, surface ECG showed a slow atrioventricular junctional rhythm in the absence of P waves in all affected relatives, and the atria could not be stimulated on invasive electrophysiologic studies. Three of them had ventricular pacemaker implantation. In this family, the entire coding region and promoter sequence of SCNSA and connexin 40 were amplified by polymerase chain reaction and analyzed by DNA sequencing, none missense mutation could be found. Conclusion This family is unambiguously affected by AS, and it may be caused by incomplete dominant inheritance of euchromosome, and another genetics mutations may contribute for AS in this family.