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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。
Objective: To study the mutation sites of pathogenic genes in Chinese patients with hypertrophic cardiomyopathy (HCM) and to analyze the relationship between genotypes and clinical phenotypes. Methods: In the HCM pedigree, 30 exon-specific genes associated with cardiomyopathy were sequenced by exon-targeted capture and sequencing method in HCM probands. All of them were sequenced by Sanger sequencing In the pedigree and 200 healthy volunteers to verify. Pedigree survey data including clinical manifestations, physical examination, electrocardiogram and echocardiography. RESULTS: Three of the six unrelated families in the pedigree carried a heterozygous mutation of MYBPC3 c. G772A gene located at 258 of MYBPC3 (E ) To lysine (K). The rest of the family members did not find this mutation. No abnormalities were found in 200 healthy volunteers. The probands and their daughters are late and have symptoms of palpitations and chest distress. Echocardiography shows thickening of the basement septum (16-18 mm). The proband is currently associated with paroxysmal ventricular tachyarrhythmias and heart failure, the maximum pressure of left ventricular outflow tract 56 mmHg (1 mmHg = 0.133 kPa), are at high risk of sudden death. Conclusion: Comprehensive genetic testing is helpful for early diagnosis and treatment of clinical risk stratification. Cleavage site mutation of MYBPC3 c.G772A may be a causative mutation in this HCM pedigree.