CENTRAL CORE DISEASE IN HYPERTROPHIC CARDIOMYOPATHY

肥厚型心肌病的核心疾病

• 批准号: 3843406
• 负责人: L FANANAPAZIR
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3843406
• 关键词: autosomal dominant trait; biopsy; bone disorder; congenital heart disorder; family genetics; gene expression; gene mutation; heavy chain disease; histopathology; human tissue; hypertrophic myocardiopathy; light microscopy; linkage mapping; muscle proteins; myocardium; myosins; striated muscles

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.

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肥厚家族中 心肌病，这种疾病与β肌球蛋白重链有关 基因位于14号染色体上。我们已经描述了几个突变 β肌球蛋白重链基因导致每种情况下的替换 一种氨基酸与另一种氨基酸的结合。我们还发现，虽然 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 在骨骼肌中也有发现。这导致了我们表演光 骨骼肌的光镜和电子显微镜检查 (腿部比目鱼肌)来自这些突变患者的活组织检查。 光学显微镜显示存在一种罕见的中央核心病 以I型为主的常染色体显性遗传性非进行性肌病 “慢”纤维和一些中央的线粒体缺失。 I型纤维。中枢性核心病和肌病在大多数 β肌球蛋白重链基因有明显突变的患者 在5名对照受试者的骨骼活检中没有检测到，在3名患有 肥厚型心肌病与 β肌球蛋白重链基因座。因此，β肌球蛋白与 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枢核心病。