病窦综合征一家系调查和有关致病基因检测

One familial sick sinus syndrome and its gene detection

目的调查家族性病窦综合征(FSSS)的发病情况及对其相关基因进行检测。方法通过分析FSSS患者的临床表现、心电图检查,利用候选基因法寻找其可能致病基因。结果此家系含有15名成员,其中有4例患者,均表现为30岁左右开始出现阵发性心房颤动、心动过缓,逐渐表现为持续性心房颤动、房室传导阻滞,其中3例已安装起搏器,遗传家系图谱提示为常染色体不完全显性遗传可能。SCN5A及HCN4的所有外显子及启动子区序列,未发现错义突变,仅发现SCN5A外显子17及HCN4外显子8的两个同义突变。结论该家系可明确诊断为FSSS;系常染色体不完全显性遗传,可能由其它一个或多个新的基因突变引起。

Objective To investigate the incidence and pathogenic genes of familial sick sinus syndrome （FSSS）. Methods To observe the clinical manifestation and electrophysiological characteristics of patients with FSSS, and detect their genes by candidate gene approach method. Results Fifteen family members were clinically evaluated, four of them were unambiguously affected by SSS. Their clinical histories were very similar, first presented with symptoms of paroxysmal atrial fibrillation and bradycardia in their early thirties. The worsened symptoms of permanent atrial fibrillation and atrioven- tricular block could be found with age. Three of them had permanent pacemaker implantation. In this family, the entire coding region and promoter sequence of SCN5A and HCN4 were amplified by polymerase chain reaction and analyzed by DNA sequencing, none missense mutation but silent mutations in the 17 exon of SCN5A and the 8 exon of HCN4 could be found. Conclusion This family is unambiguously affected by FSSS, and it is caused by incomplete dominant inheritance of euchromosome, and another genetic mutations may contribute to it.