Marian A J, Roberts R
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
J Cardiovasc Electrophysiol. 1998 Jan;9(1):88-99. doi: 10.1111/j.1540-8167.1998.tb00871.x.
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease caused by mutations in sarcomeric proteins. The disease is characterized by left ventricular hypertrophy in the absence of an increased external load, and myofibrillar disarray. A large number of mutations in genes coding for the beta-myosin heavy chain (beta-MyHC), cardiac troponin T (cTnT), cardiac troponin I, alpha-tropomyosin, myosin binding protein C (MyBP-C), and myosin light chain 1 and 2 in patients with HCM have been identified. Genotype-phenotype correlation studies have shown that mutations carry prognostic significance. The Gly256Glu, Val606Met, and Leu908Val mutations in the beta-MyHC are associated with a benign prognosis. In contrast, Arg403Gln, Arg719Trp, and Arg453Cys mutations are associated with a high incidence of sudden cardiac death (SCD). Mutations in cTnT are associated with a mild degree of hypertrophy, but a high incidence of SCD. Mutations in MyBP-C are associated with mild hypertrophy and a benign prognosis. However, it has become evident that factors other than the underlying mutations, such as genetic background and possibly environmental factors, also modulate phenotypic expression of HCM.
肥厚型心肌病（HCM）是一种由肌节蛋白突变引起的常染色体显性疾病。该疾病的特征是在没有外部负荷增加的情况下左心室肥厚以及肌原纤维排列紊乱。已在HCM患者中鉴定出大量编码β-肌球蛋白重链（β-MyHC）、心肌肌钙蛋白T（cTnT）、心肌肌钙蛋白I、α-原肌球蛋白、肌球蛋白结合蛋白C（MyBP-C）以及肌球蛋白轻链1和2的基因突变。基因型-表型相关性研究表明，这些突变具有预后意义。β-MyHC中的Gly256Glu、Val606Met和Leu908Val突变与良性预后相关。相比之下，Arg403Gln、Arg719Trp和Arg453Cys突变与心源性猝死（SCD）的高发生率相关。cTnT突变与轻度肥厚相关，但SCD发生率高。MyBP-C突变与轻度肥厚和良性预后相关。然而，已很明显，除了潜在突变外，其他因素，如遗传背景以及可能的环境因素，也会调节HCM的表型表达。
