摘要目的：研究中国汉族人群家族性肥厚型心肌病的致病基因突变，分析基因型与表型的联系。方法研究病例资料收集于2009年阜外心血管病医院门诊。利用高通量测序对1个中国汉族肥厚型心肌病家系的26个致病基因进行筛查，发现的变异通过Sanger测序验证。在家系成员中筛查发现的致病突变，对突变携带者的表型进行分析。结果包括先证者在内13例携带MYH7基因Pro731Ser错义突变，疾病与突变共分离。其他家系成员和307名正常对照未发现此突变。携带者中10例为肥厚型心肌病患者，3例为无症状携带者，患者中有8例伴有呼吸困难、心悸、胸痛、黑矇、晕厥等症状，先证者已出现严重的心力衰竭，5例患者发病年龄小于16岁，家系中至少有1人猝死。结论MYH7基因Pro731Ser错义突变为肥厚型心肌病的致病基因突变，能够产生恶性的临床表现，但也呈现明显的临床异质性。

abstractsObjective To identify the casual mutation of a Chinese pedigree with hypertrophic cardiomyopathy (HCM),and to analyze the genotype-phenotype relationship.Methods The coding exons of 26 reported disease genes were sequenced by targeted resequencing in the proband and the identified mutation were detected with bi-directional Sanger sequencing in all family members and 307 healthy controls.The genotype-phenotype correlation was analyzed in the family.Results A missense mutation (c.2191C>T, p.Pro731Ser) in the 20th exon of MYH7 gene was identified.This mutation was absent in 307 healthy controls and predicted to be pathogenic by PolyPhen-HCM.Totally 13 family members carried this mutation , including 10 patients with HCM and 3 asymptomatic mutation carriers.The proband manifested severe congestive heart failure and 8 patients expressed various clinical manifestations of heart failure , including dyspnea , palpitations , chest pain , amaurosis or syncope.Five patients were diagnosed as HCM at the age of 16 or younger.One family member suffered sudden cardiac death.Conclusions The Pro731Ser of MYH7 gene mutation is a causal and malignant mutation linked with familiar HCM.