UCLA clinical site for the investigation of undiagnosed disorders

项目摘要/摘要 未确诊的疾病对医疗保健系统和受影响的患者造成了不成比例的损失， 家人。我们的续订申请建立在我们成功帮助形成和发展当前未诊断的 疾病网络(UDN)。我们的建议加强了研究人员和医疗保健人员的协作网络 提供者，所有人都与改善医疗保健和改善受各种罕见基因影响的人的结局有关 精神错乱。我们的方法将基础和临床研究与患者护理相结合，使用尖端技术 表型技术，一系列世界级的专家，以及基因组测序到 在床边。这大大改进了罕见遗传病的诊断过程，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 将全面的基因组数据应用到临床护理中带来了相当大的挑战，从海量数据的解释 基因变异的数量与症状的相关性，与与其相关的沟通问题有关 披露，以及它们对临床管理的影响。我们的建议书描述了我们当前的UDN临床站点 和必要的修改，以过渡到在加州大学洛杉矶分校健康中心内运作的可持续临床模式 并作为正在进行的国际网络的一个组成部分，以处理纳入尖端技术的问题 将分子诊断学纳入临床工作流程，在标准化和重复性的基础上分析患者的症状 时尚，并进行研究调查，以阐明未诊断疾病的机制。我们会 通过实施以下具体目标来实现这些总体目标：目标1：维持普遍肾病诊所模式 目标2：调查新疾病和罕见疾病的临床表型； 目标3：调查新的和罕见疾病的潜在机制；目标4：建立全网络 可持续的基础设施，用于对新的和罕见的疾病进行转译研究。实体大卫·格芬 医学院的资源可用于促进可持续诊所的过渡和维持 为加州大学洛杉矶分校卫生系统、医学院和研究所提供基本服务的模式 为了精准健康。加州大学洛杉矶分校的方法是加速翻译和临床的有效模式 加州大学洛杉矶分校在改善护理提供和加强教育使命的同时进行研究。我们的项目 整合(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)和 来自所有专业领域的经验丰富的临床医生团队，(3)DNA和DNA联合讯问的专业知识 用于新基因发现的RNA测序数据；(4)环境影响调查方面的专门知识 临床症状；(5)遗传咨询和检测结果方面的专业知识；(6)获得大的、种族上的 多样化的人口和(7)可持续的方法，包括培训临床医生、遗传顾问和 基础科学家以多学科的方法解决未诊断的疾病。

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.