CENTRAL CORE DISEASE IN HYPERTROPHIC CARDIOMYOPATHY

肥厚型心肌病是最常见的遗传性心脏病， 疾病在大约三分之一到一半的肌肉肥厚 心肌病，这种疾病与β肌球蛋白重链有关 位于14号染色体上的基因。 我们已经描述了几个突变， β肌球蛋白重链基因在每种情况下导致替换 一种氨基酸被另一种氨基酸取代。 我们还发现，虽然 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和蛋白质是 也存在于骨骼肌中。 这使得我们能够 骨骼肌的显微镜和电子显微镜检查 （腿部比目鱼肌）活检与这些突变的患者。 光学显微镜检查显示存在中央核心疾病， 以I型为主的常染色体显性非进行性肌病 “慢”纤维和缺乏线粒体的中心的一些 I型纤维 中央核心病和肌病存在于大多数 β肌球蛋白重链基因有不同突变的患者， 5名对照受试者的骨骼活检和3名 肥厚型心肌病，其中疾病与 β-肌球蛋白重链基因位点。 因此，β-肌球蛋白 肥厚型心肌病是一种骨骼和心脏疾病， 肌肉和一些肥厚型心肌病患者有明显的β 肌球蛋白重链基因突变有中央核心病。

Hypertrophic cardiomyopathy is the most common inherited cardiac disease. In about a third to half of kindreds with hypertrophic cardiomyopathy, the disease is linked to the beta myosin heavy chain gene located on chromosome 14. We have described several mutations in the beta myosin heavy chain gene resulting in each case in substitution of one amino acid by another. We have also found 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 perform light microscopic and electron-microscopic examinations of skeletal muscle (soleus muscle of the leg) biopsies from patients with these mutations. Light microscopy revealed the presence of central core disease, a rare autosomal dominant non-progressive myopathy with predominance of type I "slow" fibers and absence of mitochondria from the center of some of the type I fibers. Central core disease and myopathy were present in most patients with distinct mutations in the beta myosin heavy chain gene but not in skeletal biopsies from 5 control subjects nor in 3 patients with hypertrophic cardiomyopathy in whom the disease was not linked to the beta myosin heavy chain gene locus. Thus, the beta myosin associated hypertrophic cardiomyopathy is a disease of skeletal as well as cardiac muscle and some hypertrophic cardiomyopathy patients with distinct beta myosin heavy chain gene mutations have central core disease.