UCLA clinical site for the investigation of undiagnosed disorders

项目概要/摘要 未经诊断的疾病对卫生保健系统和受影响的患者造成不成比例的损失， 家庭我们的续约申请建立在我们成功帮助形成和发展目前的未确诊 疾病网络（UDN）。我们的建议加强了研究人员和医疗保健的合作网络 提供者，所有这些都与改善受各种罕见遗传病影响的人的医疗保健和结果有关 紊乱我们的方法协同基础和临床研究和病人护理与使用尖端 表型分析技术，一系列世界级的专家，以及基因组测序的翻译， 床边这导致罕见遗传疾病的诊断过程大大改善，并促进了新的 临床实践中的发现。调查涉及多个系统的罕见疾病，并将 全面的基因组数据进入临床护理创造了相当大的挑战，从解释巨大的 基因变异的数量与其与症状的相关性，与其相关的沟通问题 披露，以及对临床管理的影响。我们的提案描述了我们目前的UDN临床研究中心 和必要的修改，过渡到一个可持续的诊所模式，在加州大学洛杉矶分校的健康功能 系统，并作为一个正在进行的国际网络的组成部分，以解决纳入最先进的 将分子诊断技术引入临床工作流程，以标准化和可重复的方式分析患者的症状， 时尚，并进行研究调查，以阐明未诊断疾病的机制。我们将 通过实施以下具体目标来实现这些总体目标：目标1：维持UDN诊所模式 目的2：研究新的和罕见的疾病的临床表型; 目的3：研究新的和罕见的疾病的潜在机制;目的4：建立一个网络范围的 可持续的基础设施，用于新的和罕见的疾病的转化研究。实质性的大卫格芬 医学院的资源可用于促进可持续诊所的过渡和维护 该模型与加州大学洛杉矶分校卫生系统，医学院和研究所一起服务于基本需求 精准健康加州大学洛杉矶分校的方法是一个有效的模式，加快翻译和临床 研究，同时改善护理服务和扩大加州大学洛杉矶分校的教育使命。我们的项目 整合了（1）加州大学洛杉矶分校临床和转化科学研究所的基础设施，（2） 来自所有专业领域的经验丰富的临床医生团队，（3）在DNA和 用于发现新基因的RNA测序数据;（4）研究环境影响的专业知识， 临床症状;（5）遗传咨询和检测结果的专业知识，（6）获得大型，种族 （7）可持续的方法，包括培训临床医生，遗传咨询师， 基础科学家在多学科的方法来解决未确诊的疾病。

Project Summary / Abstract Undiagnosed diseases take a disproportionate toll on the health care system and on affected patients and families. Our renewal application builds on our success in helping to form and grow the current Undiagnosed Diseases Network (UDN). Our proposal strengthens a collaborative network of researchers and healthcare providers, all with a stake in improving healthcare and outcomes for persons affected by various rare genetic disorders. Our approach synergizes basic and clinical research and patient care with the use of cutting-edge phenotyping technologies, an array of world class experts, and the translation of genome sequencing to the bedside. This results in a greatly improved diagnostic process for rare genetic diseases and facilitates novel discovery in clinical practice. Investigating rare diseases involving multiple systems and incorporating comprehensive genomic data into clinical care creates considerable challenges, from the interpretation of vast amounts of genetic variants to their relevance to the symptoms, to the communication issues linked to their disclosure, and to their impact on clinical management. Our proposal describes our current UDN Clinical Site and modifications necessary to transition to a sustainable clinic model that functions within the UCLA Health System and as a component of an ongoing international network to tackle the incorporation of cutting edge molecular diagnostics into the clinical workflow, analyze patients’ symptoms in a standardized and reproducible fashion, and perform research investigations to elucidate the mechanisms of undiagnosed diseases. We will reach these overarching goals by implementing the following specific aims: Aim 1: Sustain a UDN clinic model that functions locally and network-wide; Aim 2: Investigate the clinical phenotypes of new and rare disorders; Aim 3: Investigate the underlying mechanisms of new and rare disorders; Aim 4: Build a network-wide sustainable infrastructure for translational research on new and rare disorders. Substantial David Geffen School of Medicine resources are available to facilitate the transition and maintenance of the sustainable clinic model that serves an essential need with the UCLA Health System, the School of Medicine, and the Institute for Precision Health. The UCLA approach is an efficient model for accelerating translational and clinical research while improving care delivery and augmenting the educational mission of UCLA. Our project integrates the resources of (1) the infrastructure of the UCLA Clinical and Translational Science Institute, (2) an experienced team of clinicians from all specialty fields, (3) expertise in the combined interrogation of DNA and RNA sequencing data for novel gene discovery; (4) expertise in the investigation of environmental effects on clinical symptoms; (5) expertise in outcomes of genetic counseling and testing, (6) access to a large, ethnically varied population and (7) a sustainable approach that includes training clinicians, genetic counselors, and basic scientists in the multidisciplinary approach to solve undiagnosed diseases.