ABNORMAL MYOSIN IN-VITRO MOTILITY ACTIVITY IN HYPERTROPHIC CARDIOMYOPATHY

肥厚型心肌病是最常见的遗传性心脏病 是导致年轻人猝死的最重要原因。最近，一种基因 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与 我们发现一些肥厚型心肌病家系的疾病 几个家系中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，心脏蛋白也是 在骨骼组织中表达，突变的RNA和蛋白质也 在骨骼肌中发现。这让我们确定了 骨骼肌中的突变蛋白具有明显的功能异常。这个 体外运动试验测定荧光标记细胞的运动速度 肌动蛋白细丝沿着肌球蛋白结合分子滑动 表面涂有硝化棉，可用于酶-机械分析 β肌球蛋白的活性。大鼠肌球蛋白的运动活性 来自两个不同突变的患者的骨骼样本 显著低于对照受试者。因此，第一次 β肌球蛋白重链基因的独特突变已被证明 导致骨骼蛋白功能异常。

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 mutant protein in skeletal muscle has demonstrably abnormal function. The in-vitro motility assay measures the velocity of fluorescently-labelled actin filaments as they slide along myosin molecules bound to nitrocellulose-coated surface, allowing analysis of the enzymatic-mechano activity of the beta myosin. The motility activity of myosin from skeletal sample from patients with two distinct mutations were significantly less than control subjects. Thus, for the first time distinct mutations in the beta myosin heavy chain gene have been shown to result in skeletal protein with abnormal function.