心脏肌球蛋白结合蛋白C基因c.G772A突变与家族性肥厚型心肌病

发布时间：2019-03-13 17:28

【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。
[Abstract]:Aim: to study the mutation site of pathogenic gene in Chinese patients with hypertrophic cardiomyopathy (HCM) and analyze the relationship between genotype and clinical phenotype. Methods: the full exon amplification and high throughput sequencing of 30 genes associated with hereditary cardiomyopathy were performed in HCM pedigrees by targeted exon capture and sequencing. The results were further verified by Sanger sequencing in the family and in 200 healthy volunteers. Family data included clinical manifestations, physical examination, electrocardiogram and echocardiography. Results: three of the 6 unrelated subjects carried a heterozygous mutation in the cardiac myosin binding protein C gene (MYBPC3) c.G772A. The glutamic acid (E) at the 258th site of MYBPC3 was transformed into lysine (K). No mutation was found in the rest of the pedigree. No abnormalities were found in 200 healthy volunteers. The proband and his daughter were late onset with symptoms of palpitation and chest distress, and echocardiography showed a thickening of the basal segment of the ventricular septum (16 / 18 mm). The proband was accompanied by paroxysmal ventricular tachycardia with malignant arrhythmias and heart failure. The maximum pressure difference in the left ventricular outflow tract was 56 mmHg (1 mmHg=0.133 kPa), was at high risk of sudden death). Conclusion: comprehensive gene detection is beneficial to clinical risk stratification and early diagnosis and treatment. The splicing site mutation c.G772A of MYBPC 3 may be a pathogenic mutation in this HCM family.
【作者单位】：青岛市第三人民医院心内科;中国医学科学院北京协和医学院国家心血管病中心阜外医院高血压诊治中心;青岛市第三人民医院检验科;青岛市第三人民医院特检科;
【基金】：青岛市科研计划(2015-WJZD061)
【分类号】：R542.2

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