HYPERTROPHIC CARDIOMYOPATHY

肥厚型心肌病（HCM）是一种遗传性心脏病。 是 在其他方面健康的年轻人中， 个体 许多HCM患者存在左心室（LV）流出道 梗阻 我们已经证明DDD起搏器治疗可以改善 症状和缓解药物难治性患者的梗阻 症状 因此，这种新疗法是一种有吸引力的替代疗法， 心脏手术 虽然心律失常是SD最常见的原因， 在HCM成人中，我们已经确定心肌缺血， 是年轻人晕厥和心脏骤停的最常见原因 HCM患者 我们已经在β基因中发现了12种不同的突变- 肌球蛋白重链（betaMHC）基因位于14号染色体，16号染色体 不相关的运动，并估计在约20%的HCM是由它引起的 通过该基因的突变。 我们排除了β-MHC基因位点， 另外两个新的位点，在4个大家庭。 因此，我们怀疑， 有许多基因导致HCM被识别。 分子 标记物已用于鉴定没有LV肥大的个体， aMHC基因突变引起的症状和心律失常 详细 临床评估表明，疾病的自然史是 部分由特定的突变决定。 我们已经证明 突变信使RNA和β肌球蛋白存在于骨骼肌中， 受影响的患者。 含有突变的β- 肌球蛋白已经显示出具有异常的收缩特性。 贝塔- 从具有不同β MHC的患者的骨骼肌中纯化的肌球蛋白 基因突变已被证明在体外实验中具有异常功能， 运动性测定 组织化学分析表明，60%的患者 β-MHC基因突变导致骨骼肌病变--特别是"中央型" 核心病"，一种非常罕见的非进行性肌病， 一些慢肌纤维中心的线粒体。

Hypertrophic cardiomyopathy (HCM) is an inherited heart disease. It is the most common cause of sudden death (SD) in otherwise healthy young individuals. Many HCM patients have left ventricular (LV) outflow obstruction. We have demonstrated that DDD pacemaker therapy improves symptoms and relieves the obstruction in patients with drug-refractory symptoms. This novel therapy is therefore an attractive alternative to cardiac surgery. Although arrhythmias are the most common cause of SD in adults with HCM, we have determined that myocardial ischemia, often silent, is the most common cause of syncope and cardiac arrest in young HCM patients. We have identified 12 distinct mutations in the beta- myosin heavy chain (betaMHC) gene located on chromosome 14, in 16 unrelated kindreds, and estimate that in about 20% of HCM it is caused by mutations in this gene. We have excluded the betaMHC gene locus, and two other novel loci, in 4 large families. We therefore suspect that there are numerous genes that cause HCM to be identified. Molecular markers have been used to identify individuals without LV hypertrophy but with symptoms and arrhythmias caused by aMHC gene mutations. Detailed clinical evaluations indicate that the natural history of the disease is in part determined by the specific mutation. We have demonstrated that mutant messenger RNA and beta myosin are present in skeletal muscle of affected patients. Skeletal muscle myofibers containing mutant beta- myosin have been shown to have abnormal contractile properties. Beta- myosin purified from skeletal muscle of patients with distinct betaMHC gene mutations has been shown to have abnormal function in an in-vitro motility assay. Histochemical analyses show that 60% of patients with betaMHC gene mutations have skeletal myopathy--specifically, "central core disease", a very rare, nonprogressive myopathy characterized by loss of mitochondria from the center of some of the slow myofibers.