目的本研究拟查明1个中国汉族肥厚型心肌病(HCM)家系的致病突变,并探讨基因型-表型关联。方法利用二代测序技术,全面筛查家系先证者的28个HCM相关致病基因。通过Sanger测序,在家系中验证和筛查发现的可能致病突变,并对突变携带者进行表型分析。结果二代测序发现先证者携带MYH7基因Glu931del杂合突变。家系筛查发现4名患者均携带该突变,突变与疾病共分离,该突变为此HCM家系的致病突变,常染色体显性遗传。Glu931del突变位于MYH7基因第23外显子,三个核苷酸缺失(c.2791_2793del GAG),导致其所编码的心脏β-肌球蛋白重链的第931位谷氨酸缺失。MYH7基因第931位谷氨酸残基在不同物种间高度保守。临床表型分析发现,家系中4例患者的左心室最厚厚度在19mm-30mm之间,静息状态均无明显左室流出道梗阻,表现为胸痛、心悸和呼吸困难,并伴黑曚或有晕厥史。该家系另有两例患者在家系筛查前发生猝死,确诊年龄分别为5岁和6岁,死亡年龄均为16岁。该家系随访12年,HCM临床症状进展较快,1例患者左心室最大厚度由7mm发展为30mm,两例患者心功能进展为NYHA分级Ⅲ/Ⅳ级。结论 MYH7基因Glu931del突变导致的HCM表型较严重,易发生猝死和心衰,但也存在较大的表型异质性。二代高通量测序可以用于HCM致病基因的全面筛查。 Objective This study was designed to identify pathogenic mutations in a Chinese hypertrophic cardiomyopathy (HCM) pedigree and to explore genotype-phenotype associations. Methods The second generation sequencing technique was used to screen a total of 28 HCM-related pathogenic genes in pedigree probands. By Sanger sequencing, the probable pathogenic mutations found in the pedigree were validated and screened and the phenotypes analyzed for the mutation carriers. Results The second generation sequencing showed probands carry heterozygous mutation Glu931del of MYH7 gene. Family screening found that all 4 patients had this mutation, and mutations were co-segregated with the disease. The mutation was a causative mutation in the HCM pedigree with autosomal dominant inheritance. The Glu931del mutation is located in exon 23 of the MYH7 gene, with three nucleotides deleted (c.2791_2793del GAG) resulting in the deletion of the 931th glutamic acid from the beta-myosin heavy chain of the gene encoding it. The 931th glutamic acid residue of MYH7 gene is highly conserved among species. Clinical phenotype analysis found that 4 cases of family members of the left ventricular thickest thickness between 19mm-30mm, resting state no significant left ventricular outflow tract obstruction, manifested as chest pain, heart palpitations and dyspnea, accompanied by blackheads or Have a history of syncope. Two other patients in the pediatric family had sudden death before screening their families, with confirmed age of 5 years and 6 years, respectively, with a mean age of death of 16 years. The pedigree was followed up for 12 years. The clinical symptoms of HCM progressed rapidly. The maximum thickness of left ventricle in one patient increased from 7mm to 30mm. The cardiac function of two patients was NYHA class Ⅲ / Ⅳ. Conclusion The HCM phenotype induced by Glu931del mutation in MYH7 gene is more serious, sudden death and heart failure are easy to occur, but there is also a large phenotypic heterogeneity. Second-generation high-throughput sequencing can be used for comprehensive screening of HCM pathogenic genes.