【摘要】 目的:研究中国人肥厚型心肌病(HCM)患者致病基因突变位点,并分析基因型与临床表型的关系。方法:在HCM家系中利用靶向外显子捕获测序的方法对HCM先证者的30个与遗传性心肌病相关的基因进行全外显子扩增和高通量测序,进一步通过Sanger测序法在家系内及200例健康志愿者中进行验证。家系调查资料包括临床表现、体格检查、心电图及超声心动图。结果:该家系6例有血缘关系的研究对象中3例携带心脏型肌球蛋白结合蛋白C基因(MYBPC3)c.G772A杂合突变,该突变位点位于MYBPC3的258位的谷氨酸(E)变为赖氨酸(K)。其余家系成员未发现此突变。200例健康志愿者中未见异常。先证者及其女儿发病年龄晚且均伴有心悸、胸闷的症状,超声心动图示室间隔基底段增厚(16~18 mm)。先证者目前伴有阵发性室性心动过速恶性心律失常及心力衰竭,左心室流出道最大压差为56 mmHg(1 mmHg=0.133 kPa),属于猝死高危人群。结论:全面基因检测有利于临床危险分层及早诊治。MYBPC3的剪切位点突变c.G772A可能是该HCM家系的致病突变。更多还原

【Abstract】 Objective: To investigate the mutation site of pathogenic gene in patients with hypertrophic cardiomyopathy(HCM) and to analyze the relationship between the genotype and clinical phenotype.Methods: Targeted exon capture sequencing was conducted in a HCM proband for 30 coding exons related HCM gene by all exon amplification and high-throughput sequencing. Furthermore, Sanger sequencing was performed in other family member and in 200 healthy volunteers for verification. The familial investigation included in clinical presentation, physical examination, electrocardiogram and echocardiography.Results: There were 3/6 blood relatives carrying cardiac myosin-binding protein gene MyBPC3 G772A heterozygous mutation, the mutation site was at 258 amino acid of My BPC3 as glutamic acid(Glu) was substitute to lysine(Lys), such mutation was not found in rest of family member and not in healthy volunteers. The onset of proband and her daughter was rather late, they had palpitation and chest tightness; echocardiography showed interventricular septum basal segment thickening(16-18) mm. Proband was complicating paroxysmal ventricular tachycardia, malignant arrhythmia and heart failure, the maximum pressure gradient of left ventricular outflow was 56 mm Hg, which with the high risk for sudden death.Conclusion: Comprehensive gene test has been helpful for clinical stratification, early diagnosis and treatment. MYBPC3 site mutation c.G772A might be the pathogenic mutation in that specific HCM family.更多还原