Cardiomyopathies: classification, clinical characterization, and functional phenotypes.
Cardiomyopathies: classification, clinical characterization, and functional phenotypes.
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DOI：
10.1155/2012/870942
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发表时间：
2012
影响因子：
3
通讯作者：
Moore JR
中科院分区：
文献类型：
--
作者：
Szczesna-Cordary D;Morimoto S;Gomes AV;Moore JR
心肌病是一类影响心肌的疾病，可导致大量不同种族人群的广泛残疾。世界卫生组织根据解剖和生理特征将其分为三种主要类型：扩张型（DCM）、肥厚型（HCM）和限制型（RCM）。虽然DCM和RCM与进行性疾病表型、心力衰竭和猝死相关，但HCM是年轻运动员心源性猝死（SCD）的主要原因，也是影响儿童的最常见心脏病之一。本期的一篇评论文章由C。McCartan等人讨论了由于我们对许多这些临床实体的遗传和分子基础的理解的快速进步，基于形态学的心肌病传统分类是如何演变的。基因检测的影响已经被讨论为在心肌病的预后和治疗中非常有价值。作者强调，这种检测可能使临床医生超越无法解释的心室异常，识别阳性患者及其遗传原因，并预测可能的结果。在本期的另一篇评论文章中，R。Parvari和A. Levitas，它解决了遗传性DCM的发病机制。作者强烈认为，早期识别致病突变作为DCM症状前干预的想法已被证明在预防发病率和死亡率方面有价值。DCM可以是散发性的或家族性的。家族性扩张型心肌病的诊断是指发生在至少两个密切相关的家庭成员或在年轻时发生SCD。导致疾病表现的遗传因素可分为致病基因突变、单基因疾病的病因或参与多因素疾病发病机制的疾病相关基因多态性。迄今为止，编码所有主要肌节蛋白的基因中的数百个突变已被鉴定为引起HCM、DCM或RCM。这些包括对力产生（β-心肌肌球蛋白和肌动蛋白）、调节心肌收缩（原肌球蛋白和肌钙蛋白）和负责维持肌节稳定性的蛋白质（肌球蛋白结合蛋白C，肌联蛋白）必不可少的蛋白质。绝大多数心肌病突变发生在编码β-肌球蛋白重链（β-myosin heavy chain，MHC）的MYH 7基因。肌球蛋白轻链MYL 2和MYL 3分别编码调节和必需轻链的突变相对罕见，但它们也与年轻个体的恶性结果相关。事实上，大多数肌球蛋白必需轻链（ELC）突变与SCD相关。在本期的一篇文章中，PS Andersen等人在一名没有明显心脏症状的38岁HCM患者中发现了一种新的MYL 3突变V79 I（缬氨酸→异亮氨酸）。突变阳性的家庭成员也无症状，没有关于前两代SCD发生的信息。在分子水平上，该突变被预测会破坏ELC与MHC的相互作用，但未来的生物化学研究需要揭示这一可能的机制
Cardiomyopathy is a category of disorders that affect the cardiac muscle and can cause extensive disability in a large and ethnically diverse population. It has been classified by the World Health Organization into three main types, based on anatomical and physiological features: dilated (DCM), hypertrophic (HCM), and restrictive (RCM). While DCM and RCM are associated with a progressive disease phenotype, heart failure, and sudden death, HCM is the leading cause of sudden cardiac death (SCD) in young athletes and is one of the most common forms of heart diseases affecting children. One review article in this issue by C. McCartan et al. discusses how the traditional classification of cardiomyopathies based on morphology has evolved due to rapid advances in our understanding of the genetic and molecular bases for many of these clinical entities. The implications of genetic testing have been discussed as being extremely valuable in the prognosis and treatment of cardiomyopathies. The authors emphasize that such testing may allow clinicians to move beyond unexplained ventricular abnormalities, identify positive patients and their genetic cause, and predict likely outcomes. A similar need for genetic testing has been voiced in another review article in this issue, by R. Parvari and A. Levitas, which addresses the pathogenesis of hereditary DCM. The authors strongly argue that the idea of early identification of the diseasecausing mutations as presymptomatic interventions in DCM has proven valuable in preventing morbidity and mortality. DCM may be either sporadic or familial. A diagnosis of familial DCM is assigned when it occurs in at least two closely related family members or there was an occurrence of SCD at a young age. The genetic factor contributing to the manifestation of the disease can be classified either as a disease-causing gene mutation, as the etiology of monogenic disease, or as a disease-associated gene polymorphism that is involved in the pathogenesis of a multifactorial disease. To date, hundreds of mutations in genes encoding all major sarcomeric proteins have been identified to cause HCM, DCM, or RCM. These include proteins essential for force production (β-cardiac myosin and actin), regulation of cardiac muscle contraction (tropomyosin and troponin), and proteins responsible for maintaining stability of the sarcomere (myosin-binding protein C, titin). The vast majority of cardiomyopathy mutations have been found in MYH7 gene encoding the β-myosin heavy chain (MHC). Mutations in myosin light chains MYL2 and MYL3 encoding the regulatory and essential light chains, respectively, are relatively rare, but they are also associated with malignant outcomes in young individuals. In fact, most of myosin essential light chain (ELC) mutations have been associated with SCD. In one of the articles of this issue, PS Andersen et al. identified a novel MYL3 mutation, V79I (Valine→ Isoleucine), in a 38-year-old HCM patient with no visible cardiac symptoms. Mutation-positive family members were also asymptomatic, and no information was available on previous occurrences of SCD in two prior generations. At the molecular level, the mutation was predicted to disrupt the interaction of ELC with the MHC, but future biochemical studies are necessary to reveal the possible mechanism of this