SKELETAL MYOFIBER TENSION IN HYPERTROPHIC CARDIOLOGY

肥厚型心肌病是最常见的遗传性心脏病， 是年轻人猝死的最重要原因。最近，一个基因 它控制着心脏主要蛋白质β的产生 位于14号染色体上的肌球蛋白重链基因，已经与 我们发现， 几种激酶中β肌球蛋白重链基因的不同突变 患有肥厚型心肌病 我们还表明，尽管 疾病主要影响心脏，心脏蛋白也 在骨骼组织中表达，并且突变的RNA和蛋白质也 在骨骼肌中发现。 这使我们能够确定 骨骼肌中的单个肌纤维具有异常的力学功能。 由单个带皮比目鱼肌纤维产生的等距张力， 在具有已确定突变的受影响个体中测量。 这是 在几名携带突变（403ArgGln）的患者中显著降低 与恶性预后相关，但与其他突变无关。这 表明具有不同突变的肥厚型心肌病患者 在心脏β肌球蛋白重链基因可能有骨骼肌与 异常的机械性能和疾病的病理生理学 在细胞和分子水平上是不同的。

Hypertrophic cardiomyopathy is the most common inherited heart disease and is the most important cause of sudden death in the young. Recently, a gene which controls the production of the main protein of the heart, beta myosin heavy chain gene, located on chromosome 14, has been linked to the disease in some kindreds with hypertrophic cardiomyopathy, We have found distinct mutations in the beta myosin heavy chain gene in several kindreds with hypertrophic cardiomyopathy. We have also shown that although the disease affects the heart predominantly, the cardiac protein is also expressed in skeletal tissue and that the mutant RNA and protein are also to be found in skeletal muscle. This has led us to determine whether the single myofibers in skeletal muscle has abnormal mechanical function. Isometric tension generated by single skinned soleus muscle fibers was measured in affected individuals with identified mutations. This was significantly reduced in several patients with a mutation (403ArgGln) associated with a malignant prognosis but not in other mutations. This suggests that hypertrophic cardiomyopathy patients with distinct mutations in the cardiac beta myosin heavy chain gene may have skeletal muscle with abnormal mechanical properties and that the pathophysiology of the disease is varied at a cellular and molecular level.