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。我们组建了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）一个富有成效的临床和转化科学奖，主办一个大型临床研究中心 (CRC)它已经成长、发展并培养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。我们假设，我们可以使用VCUD团队将患者护理与转化研究相结合， 协同将它们与不同的VUMC资源相结合，以更有效和可持续地诊断和 治疗UD患者。我们的VCUD结构将提供测试我们的 假设和诊断并提供治疗建议。这一过渡时期的一个关键目标是 全面实施可持续发展计划（具体目标3），该计划具有包容性，并依赖于一些资源 （机构、保险计划、诺德、UDNF、慈善机构）。

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. 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 and sustainably 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. A key goal in this transition period would be to fully implement a sustainability plan (Specific Aim 3) that is inclusive and relies on a number of resources (institutional, insurance plans, NORD, UDNF, philanthropic).