摘要目的 筛查云南省一家族性肥厚型心肌病家系的致病基因突变位点,并分析其基因型与临床表型的关系.方法 入选2016年1月到云南省第一人民医院心血管内科就诊的云南省彝族一家族性肥厚型心肌病家系,共3代6人参与本研究.收集入选者的血液样本及临床资料,采用高通量测序对先证者的28个已知常见的肥厚型心肌病致病基因进行筛查,采用Sanger测序对发现的突变位点进行验证,对其家系成员及159名健康对照组人群进行检测,并分析其临床表型.结果 测序发现先证者携带β肌球蛋白重链基因(MYH7)Arg1045His和Ala26Val 2种错义突变,先证者母亲及哥哥均携带MYH7 Arg1045His突变.其他家系成员及对照组人群均未发现上述突变.该家系中肥厚型心肌病患者临床表现为胸痛、劳力性呼吸困难、晕厥,伴有明显心肌肥厚及左心室流出道梗阻,发病年龄均<50岁.先证者外祖母在调查前已发生心脏性猝死.携带双突变的先证者为家系中发病年龄最小、临床症状最严重者.结论 本研究发现云南省一家族性肥厚型心肌病家系携带MYH7 Arg1045His和Ala26Val突变,研究结果提示Arg1045His突变引起的肥厚型心肌病发病早、心肌肥厚程度严重、预后差,MYH7基因Arg1045His和Ala26Val双突变可能具有剂量效应,加重患者的临床表型.

abstractsObjective To identify the disease-causing mutations in a pedigree with familial hypertrophic cardiomyopathy (HCM) from Yunnan province, and analyze the relationship between the genotype and the phenotype.Methods The blood samples and the clinical data of the HCM family members were collected.The coding exons and their flanking intronic regions of 28 previously reported genes related to HCM were screened in the proband by high-throughput sequencing. The mutations in proband were confirmed and detected in all family members as well as in 159 healthy controls by Sanger sequencing.The relationship between the genotype and the phenotype was analyzed in this pedigree.Results Two missense mutations of Arg1045His and Ala26Val in β myosin heavy chain gene(MYH7) were identified. Genetic screening showed that the mother and brother of the proband carried Arg1045His mutation.Both mutations were absent in other family members and in 159 healthy controls.Disease onset age was less than 50 years old in this pedigree, chest pain, exertional dyspnea and syncope were the major symptoms, and all accompanied by severe left ventricular hypertrophy and left ventricular outflow tract stenosis.The grandma of the proband suffered sudden cardiac death. The proband had the worst symptoms and the earliest disease onset in this pedigree.Conclusions We find a pedigree with familial HCM from Yunnan province carrying MYH7 Arg1045His and Ala26Val mutations.The study suggests that Arg1045His mutation in MYH7 gene caused HCM is malignant with early onset, severe ventricular hypertrophy and poor prognosis. Arg1045His and Ala26Val double-mutant might have dosage effects and aggravate the clinical phenotype of the patient.