Inherited Cardiac Disease Unit, University Hospital Virgen Arrixaca, Murcia, Spain.
Internal Medicine Department, University of Murcia, Murcia, Spain.
Clin Genet. 2018 Jan;93(1):3-14. doi: 10.1111/cge.13027. Epub 2017 Aug 17.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease. HCM is a highly complex and heterogeneous disease regarding not only the number of associated mutations but also the severity of phenotype, symptom burden, and the risk of complications, such as heart failure and sudden death. The penetrance is incomplete and it is age and gender dependent. It is accepted as a disease of the sarcomere. Sixty percent of HCM cases carry mutations in 1 of 8 sarcomere protein genes, mainly non-sense MYBPC3 and missense MYH7 variants. Young patients with severe phenotype and other clinical features are included in proposed scores for prediction of high positive genetic result. The number of genes reported as disease-causing has increased in the last few years, in some cases without robust evidence. Currently available in silico tools are not always useful for differentiation between benign and deleterious variants. There is enough information on genotype-phenotype correlations to start understanding the mechanisms of the disease. Genetic and environmental modifiers have been explored with some interesting insights from miRNA studies with potential as biomarkers and therapeutic agents. There is an additional value of genetic testing in HCM for prognosis. Knowledge about genetics and functional studies are the basis of near future therapies.
肥厚型心肌病（HCM）是最常见的遗传性心血管疾病。HCM 是一种高度复杂和异质的疾病，不仅与相关突变的数量有关，而且与表型的严重程度、症状负担以及心力衰竭和猝死等并发症的风险有关。外显率不完全，且与年龄和性别有关。它被认为是一种肌节疾病。60%的 HCM 病例携带 8 种肌节蛋白基因中的 1 种突变，主要是非义 MYBPC3 和错义 MYH7 变体。年轻患者伴有严重表型和其他临床特征，被纳入预测高阳性遗传结果的评分中。在过去几年中，报告为致病的基因数量有所增加，但在某些情况下缺乏可靠的证据。目前可用的计算机工具并不总是有助于区分良性和有害变体。已经有足够的基因型-表型相关性信息来开始理解疾病的机制。遗传和环境修饰剂的研究已经有了一些有趣的见解，miRNA 研究具有作为生物标志物和治疗剂的潜力。HCM 进行基因检测对预后有额外的价值。对遗传学和功能研究的了解是未来治疗的基础。
