Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited myocardial disease characterized by unexplained left ventricular hypertrophy, diastolic dysfunction and myocardial disarray. Clinical heterogeneity is wide, ranging from asymptomatic individuals to heart failure, arrhythmias and sudden death. HCM is often caused by mutations in genes encoding components of the sarcomere. Among them, MYBPC3, encoding cardiac myosin-myosin binding protein C is the most frequently mutated gene. Three quarter of pathogenic or likely pathogenic mutations in MYBPC3 are truncating and the resulting protein was not detected in HCM myectomy samples. The overall prognosis of the patients is excellent if managed with contemporary therapy, but still remains a significant disease-related health burden, and carriers with double heterozygous, compound heterozygous and homozygous mutations often display a more severe clinical phenotype than single heterozygotes. We propose these individuals as a good target population for MYBPC3 gene therapy.

肥厚性心肌病 (HCM) 是最常见的遗传性心肌病，其特征是无法解释的左心室肥厚、舒张功能障碍和心肌紊乱。临床异质性广泛，从无症状个体到心力衰竭、心律失常和猝死。HCM 通常是由编码肌节成分的基因突变引起的。其中，编码心肌肌球蛋白-肌球蛋白结合蛋白C的MYBPC3是突变频率最高的基因。MYBPC3 中四分之三的致病或可能致病突变正在截断并且在 HCM 肌切除术样本中未检测到产生的蛋白质。如果采用现代疗法进行治疗，患者的总体预后良好，但仍然是与疾病相关的重大健康负担，并且具有双杂合子、复合杂合子和纯合子突变的携带者通常比单杂合子显示出更严重的临床表型。我们建议将这些个体作为MYBPC3基因治疗的良好目标人群。