Long QT Syndrome: Population, Genetic & Cardiac Studies

描述（由申请方提供）：拟定的研究是一项多学科、多中心、协作研究，旨在继续研究长QT综合征（LQTS）的临床、心脏和遗传方面-一种遗传性通道病，伴有心室复极延迟和阵发性恶性心律失常，表现为晕厥和猝死。目前，已在LQTS中鉴定了6个离子通道基因（KCNQ 1，HERG，SCNhA，minK，MIRP 1和KCNJ 2）上的300多个突变。这项为期五年的研究活动将：1）继续升级，扩大和收集900个活跃的LQTS家庭的临床和遗传数据（5，508名活跃的家庭成员）目前登记在LQTS登记处; 2）使用不同的时间起点开发多变量预后风险评分系统（从出生开始，从10岁，20岁和40岁开始）; 3）评估LQTS疗法的有效性和局限性; 4）扩大对LQTS基因型-表型关系的研究。在功能上，该基金有四个部分：临床部分，涉及六个临床中心，这些中心已经登记并积极跟踪登记处的LQTS家族;基因型部分，涉及四个经验丰富的分子遗传实验室;生物统计部分，将提供研究设计和统计数据分析方面的专业知识;以及一个中央协调和数据中心，将提供数据管理和协调该计划的各个组成部分。这一综合研究项目提供了一个实质性的前景：1）提高诊断，管理和治疗受LQTS影响的个人;和2）提供一个基本的了解复极相关的心律失常的分子基础的患者与广泛的心脏疾病。

DESCRIPTION (provided by applicant): The proposed research is a multidisciplinary, multicenter, collaborative study to continue the investigation of the clinical, cardiac, and genetic aspects of the Long QT Syndrome (LQTS) - a heritable channelopathy with delayed ventricular repolarization and episodic malignant arrhythmias manifest by syncope and sudden death. Presently, over 300 mutations on 6 ion-channel genes (KCNQ1, HERG, SCNhA, minK, MIRP1, and KCNJ2) have been identified in LQTS. The five-year research activity will: 1) continue to upgrade, expand, and collect clinical and genetic data on 900 active LQTS families (5,508 active family members) currently enrolled in the LQTS Registry; 2) develop a multivariate prognostic risk-scoring system using different time origins (from birth, and from age 10, 20, and 40 years); 3) evaluate the effectiveness and limitations of LQTS therapies; and 4) expand investigations into LQTS genotype-phenotype relationships. Functionally, the grant has four sections: a clinical section involving six clinical centers that have enrolled and are actively following the LQTS families in the Registry; a genotype section involving four experienced molecular genetic laboratories; a biostatistical section that will provide expertise in study design and statistical data analyses; and a central coordination and data center that will provide data management and coordination of the various components of the program. This integrated research program offers a substantial prospect of: 1) improving the diagnosis, management, and treatment of individuals affected with LQTS; and 2) providing a fundamental understanding of the molecular basis of repolarization-related cardiac arrhythmias in patients with a broad spectrum of cardiac disorders.