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。UDN的加州大学洛杉矶分校临床站点行政补充支持正在进行的工作 UDN是一个研究人员和医疗保健提供者的合作网络，所有这些都与改进 各种罕见遗传疾病患者的医疗保健和结果，以及通向可持续发展的桥梁 加州大学洛杉矶分校临床站点的临床模式。我们的方法将基础和临床研究与患者护理相结合 通过使用尖端的表型技术，一系列世界级的专家，以及翻译的 把基因组测序送到床边。这大大改进了罕见基因的诊断过程 并促进临床实践中的新发现。调查涉及多个领域的罕见病 系统和将全面的基因组数据纳入临床护理带来了相当大的挑战， 从对大量基因变异的解释到它们与症状的相关性，再到 与他们的披露相关的沟通问题，以及他们对临床管理的影响。这个 UDN的加州大学洛杉矶分校临床网站的行政补充支持与 参与者及其家人以及完成了利用UDN发现基因/疾病的启动工作 合作者。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： 实施在本地和网络范围内发挥作用的UDN诊所模式；目标2：调查临床 新疾病和罕见疾病的表型；目标3：研究新疾病和罕见疾病的潜在机制 障碍；目标4：建立网络范围的可持续基础设施，用于对新的和罕见的疾病进行翻译研究 精神错乱。加州医学中心提供大量的大卫·格芬医学院资源 罕见疾病促进可持续临床模式的过渡和维护 加州大学洛杉矶分校卫生系统、医学院和精密卫生研究所的基本需求。 加州大学洛杉矶分校的方法是一种有效的模式，可以加速翻译和临床研究，同时改进 提供关怀和加强加州大学洛杉矶分校的教育使命。我们的项目整合了(1) 加州罕见病中心的基础设施，(2)一支经验丰富的临床医生团队 专业领域，(3)新基因的DNA和RNA测序数据的联合询问的专业知识 发现；(4)调查环境对临床症状的影响的专门知识；(5) 遗传咨询和检测的结果，(6)获得大量不同种族人口的机会和(7) 可持续的方法，包括培训临床医生、遗传咨询师和基础科学家 解决未确诊疾病的多学科方法。

Project Summary / Abstract Undiagnosed diseases take a disproportionate toll on the health care system and on affected patients and families. The Administrative Supplement for the UCLA Clinical Site of the UDN supports ongoing work within the UDN, 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, and bridges to a Sustainable Clinic Model for the UCLA Clinical Site. 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. The Administrative Supplement of the UCLA Clinical Site of the UDN supports ongoing communications with participants and their families and completion of initiated work on gene/disease discovery with UDN collaborators. We will reach these overarching goals by implementing the following specific aims: Aim 1: Implement 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 within the California Center for Rare Diseases 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 California Center for Rare Diseases, (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.