Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts, USA.
Ann Intern Med. 2010 Apr 20;152(8):513-20, W181. doi: 10.7326/0003-4819-152-8-201004200-00008.
Unexplained cardiac hypertrophy, the diagnostic criterion for hypertrophic cardiomyopathy (HCM), occurs in 1 in 500 adults. Insights into the genetic cause and molecular pathophysiology of HCM are reshaping clinical paradigms for diagnosis and treatment of this common myocardial disorder. Human genetic studies have established that dominant mutations in the proteins that make up the contractile apparatus (the sarcomere) cause HCM. With the current availability of clinical gene-based diagnostics, pathogenic mutations in affected patients can be defined, which can suggest a clinical course and allow definitive preclinical identification of family members at risk for HCM. Genetic discoveries have also fostered mechanistic investigations in model organisms that are engineered to carry human HCM mutations. Novel therapeutic targets have emerged from these fundamental studies and are currently under clinical assessment in humans. The combination of contemporary gene-based diagnosis with new strategies to attenuate disease development and progression is changing the natural history of lifelong cardiac symptoms, arrhythmias, and heart failure from HCM.
不明原因的心脏肥大是肥厚型心肌病（HCM）的诊断标准，每 500 个成年人中就有 1 个会出现这种情况。对 HCM 的遗传原因和分子病理生理学的深入了解正在改变这种常见心肌疾病的诊断和治疗临床范例。人类遗传学研究已经证实，构成收缩装置（肌节）的蛋白质中的显性突变会导致 HCM。随着目前临床基于基因的诊断的可用性，可以确定受影响患者的致病性突变，这可以提示临床病程，并允许明确鉴定出患有 HCM 风险的家族成员。遗传发现还促进了携带人类 HCM 突变的模型生物的机制研究。这些基础研究产生了新的治疗靶点，目前正在人体中进行临床评估。将当代基于基因的诊断与减轻疾病发展和进展的新策略相结合，正在改变 HCM 患者终生心脏症状、心律失常和心力衰竭的自然病史。
