心脏型肌球蛋白结合蛋白C基因缺失突变导致肥厚型心肌病特点分析

目的观察肥厚型心肌病（HCM）患者心脏型肌球蛋白结合蛋白C基因（MYBPC3）缺失突变及其表型的特点。方法在100例HCM患者中对MYBPC3的所有外显子及其侧翼内含子序列进行基因扫描,聚合酶链反应（PCR）扩增目的片段,双脱氧末段终止法测序。对突变患者进行家系调查,分析其表型特点。结果在两例先证者中分别发现两个缺失突变14262_14264delAAG和14364delG,均位于外显子25。表型分析发现两例先证者均有劳力性胸闷、胸痛和晕厥史,超声心动图表现为不对称性肥厚（室间隔/左室后壁分别为2.5、3.2）,但SAM征阴性,发病年龄分别为38岁和29岁。结论缺失突变是MYBPC3基因突变的常见形式,14262_14264delAAG或14364delG突变导致的HCM表现为不对称性心肌肥厚,患者容易出现晕厥等症状,应该警惕心源性猝死的发生。

Analysis of Genotype-Phenotype in Chinese Hypertrophic Cardiomyopathy Patients Associated with MYBPC3 Deletion Mutation

Objective To describe the characteristic of hypertrophic cardiomyopathy in Chinese patients associated with MYBPC3 deletion mutation.Methods A systematic mutation screening of the whole exons and the adjacent introns of MYBPC3 gene was performed in 100 unrelated Chinese adult patients with HCM using direct DNA sequencing.The phenotype of the HCM patients and their family members was analyzed.Results Two mutations（14262_14264delAAG and 14364delG）,both located in the exon 25 of MYBPC3,were identified in two index patients with HCM respectively.The both probands expressed dyspnea or chest pain on exertion,syncope,and asymmetric septal hypertrophy in echocardiography.The rario of septal-to-posterior wall thickness was 2.5 in patient associated with 14262_14264delAAG and 3.2 in patient associated with 14364delG.The onset-age was 38 years in patient carried 14262_14264delAAG mutation and 29 years in patient carried 14364delG mutation.Conclusion Deletion mutation was the common feature of MYBPC3 mutation in Chinese patients with HCM.The mutation 14262_14264delAAG or 14364delG in MYBPC3 gene might result in asymmetric septal hypertrophy and syncope in HCM patients.The two patients should undergo comprehensive sudden cardiac death risk stratification.