Vanderbilt Center for Undiagnosed Diseases (VCUD)

项目摘要 未诊断的疾病（UD）是观察到的显著体征，症状和/或测试结果的星座 专家长期以来没有发现其原因，并且诊断程序和测试已经 筋疲力尽未诊断疾病网络（UDN）的目标是诊断UD并提供答案 给受折磨的人带来希望和改善健康的方法。我们的范德比尔特UDN临床研究中心（VCUD） 是一个优秀的病人为导向的护理和合作研究的理想环境。我们成立了VCUD， 将独特的范德比尔特资源与UDN资源相结合以诊断困难的UD。范德比尔特资源 包括：1）富有成效的临床和转化科学奖，其中设有一个大型临床研究中心 (CRC)它已经成长，发展和发展了一批杰出的临床医生和医生科学家，2） 一个由儿科医生、内科医生、神经学家和遗传学家组成的强大而专注的团队，生物信息学专家， 4)BioVU DNA数据库和专家，5）结构生物学研究人员，6）我们的EMR和REDCap 数据库，以及7）高度重视教育和培训下一代，他们将有助于维持UDN 从长远来看。我们将我们的VCUD团队（医生、生物信息学专家、研究人员） 科学家，研究协调员，NP，GC），利用UDN资源通过以下方式诊断UD患者：A） 收集和分析临床数据以形成鉴别诊断（临床假设），B）接着分析 世代测序和其他测试数据以形成可测试的基因假设，C）利用独特的VUMC 包括BioVU、PrediXcan和结构生物学在内的资源，以优先考虑候选变体（CV），D） 确定非编码CV的功能效应，E）测试并将我们的临床和遗传 用于识别导致患者UD的一致性疾病和CV的假设，和F）使用VCUD Studios 发现新的疾病，促进转化研究，以确定机制， 治疗。使用这种方法，我们已经诊断出39/50 UDN的情况下，我们的VCUD评估的日期。我们 假设我们可以使用VCUD团队，通过协同方式将患者护理与转化研究合并， 将它们与不同的VUMC资源相结合，以更有效地诊断和治疗UD患者。我们的VCUD 结构将提供测试我们的假设和诊断所需的工作流程，吞吐量和激情， 提供治疗建议。我们会在第二阶段扩展计划（UO 1）中加强所有这些活动 通过与UDN、退伍军人管理局、精准医学项目和医疗保健的合作， 保险公司，以产生一个不断发展和更可持续的模式。因此，我们将加速合并患者 以转化研究为导向的专业护理，以改善诊断，护理和理解 我们的具体目标是：1）改善所有年龄段UD患者的诊断和护理，2） 确定UD的原因并改进UD的治疗方案，以及3）测试BioVU和 结构生物学可以作为一种综合方法来识别UDN患者的致病变异。 !

Project Summary Undiagnosed Diseases (UD) are constellations of significant signs, symptoms and/or test results that are seen by specialists over time without discovery of their cause(s), and for which diagnostic procedures and tests have been exhausted. The goal of the Undiagnosed Disease Network (UDN) is to diagnose UDs and bring answers that give afflicted individuals hope and ways to improve their health. Our Vanderbilt UDN Clinical Site (VCUD) is an ideal milieu of excellent patient oriented care, and collaborative research. We formed the VCUD by combining unique Vanderbilt resources with UDN resources to diagnose difficult UDs. Vanderbilt resources include: 1) a productive Clinical and Translational Science Award that hosts a large Clinical Research Center (CRC) that has grown, evolved, and developed an outstanding cohort of clinicians and physician scientists, 2) a strong, dedicated group of Pediatricians, Internists, Neurologists and Geneticists, 3) bioinformatics experts, 4) the BioVU DNA databank and experts, 5) structural biology investigators, 6) our EMR and REDCap database, and 7) a strong focus on educating and training the next generation who will help sustain the UDN over the long-term. We have combined our VCUD team (physicians, bioinformatics experts, research scientists, Study Coordinator, NPs, GCs), with UDN resources to diagnose UD patients by the following: A) gathering and analyzing clinical data to form differential diagnoses (clinical hypotheses), B) analyzing next generation sequencing and other test data to form testable gene hypotheses, C) utilizing unique VUMC resources including BioVU, PrediXcan, and Structural Biology to prioritize candidate variants (CV), D) determining the functional effects of non-coding CV, E) testing and merging our clinical and genetic hypotheses to identify concordant disorders and CV that cause the patients' UD, and F) using VCUD Studios to discover new diseases and promote translational research to determine mechanisms and lead to treatments. Using this approach, we have diagnosed 39/50 UDN cases evaluated by our VCUD to date. We hypothesize that we can use VCUD teams to merge patient care with translational research by synergistically combining them with distinct VUMC resources to more efficiently diagnose and treat UD patients. Our VCUD structure will provide the workflow, throughput, and passion needed to test our hypotheses and diagnose and provide treatment recommendations. We will enhance all these activities in the Phase II (UO1) expansion through collaborations with the UDN, the Veteran's Administration, Precision Medicine Projects and health care insurers, to produce an evolving and more sustainable model. Thus, we will accelerate merging patient oriented specialty care with translational research to improve the diagnosis, care, and understanding of patients with UD by our specific aims to: 1) Improve the diagnosis and care of UD patients of all ages, 2) Determine causes of and improve treatment options for UD, and 3) Test the hypothesis that BioVU and Structural Biology can be used as an integrated approach to identify causative variants in UDN patients. !