FAMILIAL DILATED CARDIOMYOPATHY--DETECTION/GENE MAPPING

描述：(改编自《调查者摘要》)心力衰竭是 只有重大心血管疾病的发病率和患病率增加 在美国，它影响了200多万公民。心力衰竭 导致大量的发病率，携带高死亡率和消耗 相当可观的卫生保健资源。心力衰竭是最单一的 医疗融资中的昂贵诊断相关组(DRG 127) 行政(HCFA)医疗保险预算(1992年数据)，大部分到期 老年美国人心力衰竭的高发病率和盛行率。 尽管公共卫生问题日益加剧，代价高昂，但20年来 密集的基础和临床研究并没有产生统一的 心脏的病理生理学概念和潜在的分子机制 失败仍是未知数。最常见的心力衰竭类型是扩张型。 心肌病，一种常见的形式是特发性扩张型心肌病 (IDC)。最近有研究表明，20%-30%的IDC患者 家庭成员也受到了类似的影响。这种情况称为家族性扩张症 心肌病(FDC)，提示潜在的分子机制可能是 牵涉其中。事实上，最近有四个群体报告了大范围的关联 FDC家系，提示FDC可能是一种遗传性疾病。这个 应用表明，识别与疾病相关的基因可能 极大地提高了对心脏机制的理解 失败了。自1993年以来，俄勒冈健康科学大学(OHSU) 前瞻性地确定了许多患有FDC的家庭。应用程序 建议选择三个大的家系将有助于 临床和基因图谱研究。这个项目的具体目标是 到：1)进行广泛的临床筛查和OHSU的特征 FDC-3，一个患有扩张型心肌病的非常大的非裔美国人家庭， 使用超声心动图得出的左心室内径进行分类 受影响或不受影响的成员。到目前为止，没有其他非洲裔美国人 家族的特征是FDC。美国黑人示威 相当高的心血管死亡率，传统上 在临床研究中的代表性不足；以及2)定位一个或多个基因 负责OHSU家族FDC-1、FDC-2和FDC-3的FDC。初步 数据显示，OHSU FDC-1与最近报告的这两种病毒都没有关联 心肌病的染色体位置，提示一个额外的基因座 因为FDC是存在的。

DESCRIPTION: (Adapted from Investigator's Abstract) Heart failure is the only major cardiovascular diagnosis increasing in incidence and prevalence in the U.S., and it affects more than two million citizens. Heart failure causes a great deal of morbidity, carries a high mortality rate and consumes considerable health care resources. Heart failure is the single most expensive diagnosis related group (DRG 127) in the Health Care Financing Administration (HCFA) Medicare budget (1992 data), due in substantial part to the high incidence and prevalence of heart failure in aging Americans. Despite this accelerating and costly public health problem, two decades of intensive basic and clinical investigations have not yielded a unifying pathophysiological concept, and the underlying molecular mechanisms of heart failure are still unknown. The most common type of heart failure is dilated cardiomyopathy, and one common form is idiopathic dilated cardiomyopathy (IDC). It has recently been shown that 20-30% of patients with IDC have family members similarly affected. This condition, termed familial dilated cardiomyopathy (FDC), suggests that an underlying molecular mechanism may be involved. Indeed, four groups have recently reported linkage in large families with FDC, suggesting that FDC is likely a genetic disease. The application suggests that identification of a disease-associated gene could provide a significant improvement of understanding the mechanisms of heart failure. Since 1993, the Oregon Health Sciences University (OHSU) has prospectively identified numerous families with FDC. The application suggests that the selection of three large pedigrees would be useful for clinical and gene mapping studies. The Specific Aims of this project are to: 1) perform extensive clinical screening and characterization of OHSU FDC-3, a very large African-American family with dilated cardiomyopathy, using echocardiographically-derived left ventricular dimensions to classify members as affected or non-affected. To date, no other African-American family has been characterized with FDC. Black Americans demonstrate considerable excess cardiovascular mortality and have traditionally been underrepresented in clinical research; and 2) map the gene or genes responsible for FDC in OHSU families FDC-1, FDC-2 and FDC-3. Preliminary data suggest that OHSU FDC-1 links to neither of the recently reported cardiomyopathy chromosomal locations, suggesting that an additional locus for FDC is present.