Department of Medicine, Division of Cardiovascular Diseases, and the Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN 55905, USA.
Circulation. 2010 Dec 7;122(23):2441-9; discussion 2450. doi: 10.1161/CIRCULATIONAHA.110.954446.
Hypertrophic cardiomyopathy (HCM), or clinically unexplained hypertrophy of the heart, is a common genetic cardiovascular disorder marked by genetic and phenotypic heterogeneity. As the genetic mutations underlying the pathogenesis of this disease have been identified, investigators have attempted to link mutations to clearly defined alterations in survival in hopes of identifying prognostically relevant biomarkers of disease. While initial studies labeling particular -encoded beta myosin heavy chain and -encoded cardiac troponin T mutations as “malignant” or “benign” raised hopes for mutation-specific risk stratification in HCM, a series of subsequent investigations identified mutations in families with contradictory disease phenotypes. Furthermore, subsequent proband-based cohort studies indicated that the clinical prognostic relevance of individual mutations labeled as “malignant” or “benign” in large referral centers is negligible. Herein, we seek to summarize the controversy and dispute the notion that mutation-specific risk stratification in HCM is possible at the present time. We provide evidence for clinicians and basic scientists alike to move beyond simple mutation descriptors to a more nuanced understanding of HCM mutations that fully captures the multi-factorial nature of HCM disease expression.
肥厚型心肌病（HCM），或临床上无法解释的心脏肥厚，是一种常见的遗传性心血管疾病，其特征为遗传和表型异质性。随着导致该疾病发病机制的基因突变的确定，研究人员试图将突变与明确定义的生存改变联系起来，以期确定疾病的预后相关生物标志物。虽然最初的研究将特定的肌球蛋白重链编码基因和肌钙蛋白 T 编码基因突变标记为“恶性”或“良性”，从而为 HCM 的突变特异性风险分层带来了希望，但随后的一系列研究确定了在具有矛盾疾病表型的家族中的突变。此外，随后的基于先证者的队列研究表明，在大型转诊中心中被标记为“恶性”或“良性”的个体突变的临床预后相关性可以忽略不计。在此，我们试图总结争议，并驳斥目前在 HCM 中进行突变特异性风险分层是可能的观点。我们为临床医生和基础科学家提供了证据，使他们能够超越简单的突变描述符，对 HCM 突变有更细致的理解，从而充分捕捉 HCM 疾病表达的多因素性质。
