Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and is characterized by asymmetric left ventricular hypertrophy and diastolic dysfunction, and a frequent cause of sudden cardiac death at young age. Pharmacological treatment to prevent or reverse HCM is lacking. This may be partly explained by the variety of underlying disease causes. Over 1500 mutations have been associated with HCM, of which the majority reside in genes encoding sarcomere proteins, the cardiac contractile building blocks. Several mutation-mediated disease mechanisms have been identified, with proof for gene- and mutation-specific cellular perturbations. In line with mutation-specific changes in cellular pathology, the response to treatment may depend on the underlying sarcomere gene mutation. In this review, we will discuss evidence for mutation-specific pathology and treatment responses in HCM patients, mouse models and engineered heart tissue. The pros and cons of these experimental models for studying mutation-specific HCM pathology and therapies will be outlined.

中文翻译：

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患者，小鼠模型和人类工程心脏组织的突变特异性病理学和肥厚型心肌病的治疗。

肥厚型心肌病（HCM）是最常见的遗传性心肌病，其特征是左心室不对称肥大和舒张功能障碍，并在年轻时常导致心源性猝死。缺乏预防或逆转HCM的药物治疗方法。可能由多种潜在的疾病原因部分解释了这一点。与HCM相关的突变超过1500个，其中大多数位于编码肌收缩蛋白的肌节蛋白的基因中。已经确定了几种突变介导的疾病机制，并证明了基因和突变特异性细胞的扰动。与细胞病理学中特定于突变的变化相一致，对治疗的反应可能取决于潜在的肌节基因突变。在这篇评论中 我们将讨论HCM患者，小鼠模型和心脏工程组织中特定于突变的病理学和治疗反应的证据。将概述这些研究突变特异性HCM病理学和疗法的实验模型的优缺点。