FAMILIAL DILATED CARDIOMYOPATHY--DETECTION/GENE MAPPING

描述：（改编自研究者摘要）心力衰竭是 只有重大心血管诊断的发病率和患病率增加 在美国，它影响了超过两百万的公民。 心力衰竭 造成大量的发病率，死亡率高，消耗 大量的医疗资源。 心力衰竭是最常见的 医疗保健融资中的昂贵诊断相关组（DRG 127） 医疗保健预算（1992年数据），大部分到期 老年美国人心力衰竭的高发病率和患病率。 尽管这一加速和昂贵的公共卫生问题，二十年来， 密集的基础和临床研究尚未产生统一的 病理生理学概念和心脏的潜在分子机制 失败仍然是未知的。 最常见的心力衰竭类型是扩张型 一种常见的形式是特发性扩张型心肌病 （IDC）。 最近的研究表明，20-30%的IDC患者 家庭成员同样受到影响。 这种情况，称为家族性扩张 心肌病（FDC），表明一个潜在的分子机制可能是 涉案 事实上，最近有四个团体报告说， FDC家族，这表明FDC可能是一种遗传性疾病。 的 应用表明，疾病相关基因的鉴定可以 为我们理解心脏的机制提供了重要的帮助 失败 自1993年以来，俄勒冈州健康科学大学（OHSU） 前瞻性地确定了许多患有FDC的家庭。 应用 这表明，选择三个大的谱系将是有用的， 临床和基因定位研究。 该项目的具体目标是 目的：1）对OHSU进行广泛的临床筛选和表征 FDC-3，一个患有扩张型心肌病的非洲裔美国大家族， 使用超声心动图导出的左心室尺寸来分类 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 家族的特征为FDC。 美国黑人示威 心血管死亡率相当高，传统上 在临床研究中代表性不足; 2）绘制基因或基因图谱 负责OHSU系列FDC-1、FDC-2和FDC-3中的FDC。 初步 数据表明，OHSU FDC-1与最近报道的 心肌病的染色体位置，表明一个额外的基因座， 的FDC存在。

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.