Multidisciplinary Study of Right Ventricular Dysplasia

右心室发育不良的多学科研究

• 批准号: 6527074
• 负责人: FRANK I MARCUS
• 金额: $ 65.36万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-27 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527074
• 关键词: arrhythmia; cooperative study; diagnosis design /evaluation; family genetics; gene expression; gene mutation; genetic mapping; genetic susceptibility; heart disorder diagnosis; heart function; heart ventricle; human subject; longitudinal human study; pathologic process; patient /disease registry; patient oriented research

DESCRIPTION (provided by applicant): This application is part of a clustered proposal consisting of three components: an application by Dr. Frank Marcus describing the overall scientific program, an application by Dr. Jeffrey Towbin describing the genetic analyses for the study, and a proposal by Dr. Wojciech Zareba describing the organization and operation of the Coordination and Data Center (CDC) for the study. The proposed five-year research plan is a multi-disciplinary, multicenter, collaborative study to investigate the cardiac, clinical, and genetic aspects of arrhythmogenic right ventricular dysplasia (ARVD), a progressive disorder that predominantly affects the right side of the heart and causes ventricular arrhythmias. In many patients the disease is familial. ARVD may account for as many as 5% of unexpected sudden deaths under the age of 65 and 3-4% of sudden death during sports. There can be considerable difficulty in diagnosing this disease with certainty, and there is incomplete information on the pathogenesis, natural history, and treatment of the patients and affected members. The overall objective of the Multidisciplinary Study of Right Ventricular Dysplasia is to characterize the genetic and clinical features of arrhythmogenic right ventricular dysplasia (ARVD). The specific aims are: 1) to establish a North American ARVD Registry enrolling ARVD patients and their family members, based on standardized diagnostic test criteria, in a prospective longitudinal follow-up study; 2) to determine the genetic background of ARVD by identifying chromosomal loci and specific gene mutations associated with this disorder; 3) to determine the influence of the genotype on the clinical course of patients with ARVD and explore phenotype-genotype associations that will contribute to improved diagnosis, risk stratification, and therapy; and 4) to develop quantitative methods to assess right ventricular function in order to enhance the specificity and sensitivity of ARVD diagnosis. This integrated research grant proposal offers a substantial prospect of expanding the fund of clinical knowledge regarding ARVD and of localizing the gene(s) responsible for this disorder.

描述（由申请人提供）： 该应用程序是由三个组成的集群建议的一部分 组件：弗兰克·马库斯（Frank Marcus）博士的申请，描述了总体 科学计划，杰弗里·托宾（Jeffrey Towbin）博士的申请描述 该研究的遗传分析，以及Wojciech Zareba博士的提案 描述协调和数据中心的组织和运营 （CDC）进行研究。拟议的五年研究计划是一个多学科的研究， 多中心，协作研究以调查心脏， 心律失常右心发育不良的临床和遗传方面 （ARVD），一种进行性疾病，主要影响 心脏并引起心室心律不齐。在许多患者中，这种疾病是 家族。 ARVD可能占意外突然死亡的5％ 运动中突然死亡的65岁和3-4％的年龄在65岁以下。可以 确定诊断这种疾病的困难，那里 是关于发病机理，自然病史和治疗的不完整信息 患者和受影响的成员。总体目标 右心发育不全的多学科研究是为了表征 心律失常右心发育不良的遗传和临床特征 （ARVD）。具体目的是：1）建立北美ARVD 根据注册表招生ARVD患者及其家人的注册 标准化的诊断测试标准，在前瞻性纵向随访中 学习; 2）通过识别ARVD的遗传背景 染色体基因座和与该疾病相关的特定基因突变； 3）确定基因型对临床过程的影响 ARVD和探索表型基因型关联的患者 有助于改善诊断，风险分层和治疗；和4）到 开发定量方法来评估右心室功能，以便 提高ARVD诊断的特异性和灵敏度。这整合了 研究赠款提案提供了扩大基金的巨大前景 有关ARVD和本地化基因负责的临床知识 对于这种疾病。