Washington University School of Medicine Undiagnosed Diseases Network Clinical Site

1.0项目总结 这一应用的科学前提是， 在第一阶段开发的未诊断疾病网络(UDN)是可扩展的，其对患者的影响， 家庭，疾病发现可以通过在华盛顿增加一个临床站点来推进和维持 医学院(WUSM)。WUSM代表着一个大型学术医疗中心，它完全 与世界知名的基础科学能力相结合，并在基因优先方法中展示了专业知识 适用于有未确诊疾病的患者。高度协作的临床和生物医学研究文化 WUSM促进部门内部和跨部门的互动，与机构基因组、临床、计算、 和模型系统专家，以及与地区、国家和国际的同行。这些相互作用 支持儿童和成人患者的招募、选拔、评估、诊断发现和随访 通过已建立的网络和个人转诊来诊断未诊断的疾病。在这个基础设施的基础上， WUSM教职员工将推动UDN在#年诊断和管理疾病方面的成功 未诊断的患者，首先，使用、改进和改进在第一阶段设计的方案 每年对30名未确诊患者进行全面、及时的临床评估。其次，我们 将收集、安全存储和共享标准化、高质量的临床和实验室数据，包括 基因分型、表型分型和环境暴露记录，并促进综合和 整个UDN以及实验室和临床研究人员之间的协作社区，专注于 明确导致这些疾病难以诊断的病理生理学、细胞生物学和分子机制 疾病。第三，WUSM UDN临床站点将提出一个生物信息学计划，以利用机构 基础设施和专门知识，以制定创新战略，以改进致病变种的发现。 第四，评估、传播、外联和培训计划将加快评估和 传播数据、协议、同意材料和方法、提供教育和外联服务 参与者、临床医生和其他研究人员的材料，未被充分代表的少数民族的参与，以及 与WUSM的临床和转化科学合作对学生、研究员、工作人员和教职员工进行培训 奖励基础设施。最后，WUSM将做出明确的制度承诺，以维持其临床 网站，以适应可持续发展的UDN第一阶段做法，为形成可持续的国家 UDN资源，并适应独特的需求和可能出现的意外情况 共同基金的支助在2022财政年度结束。

1.0 PROJECT SUMMARY The scientific premise of this application is that the individualized translational research process of the Undiagnosed Diseases Network (UDN) developed during Phase I is scalable and that its impact on patients, families, and disease discovery can be advanced and sustained by addition of a Clinical Site at Washington University School of Medicine (WUSM). WUSM represents a large academic medical center that is fully integrated with world-renowned basic science capabilities and demonstrated expertise in a gene first approach for patients with undiagnosed diseases. The highly collaborative clinical and biomedical research culture at WUSM promotes interactions within and across Departments, with institutional genomic, clinical, computational, and model system experts, and with colleagues regionally, nationally, and internationally. These interactions support recruitment, selection, evaluation, diagnosis discovery, and follow up of pediatric and adult patients with undiagnosed diseases through both established networks and individual referrals. Building on this infrastructure, WUSM faculty and staff will advance the success of the UDN in diagnosing and managing disease in undiagnosed patients by, first, using, refining, and improving protocols designed during Phase I of the UDN for comprehensive, timely clinical evaluations of 30 undiagnosed patients annually. Secondly, we will collect, securely store, and share standardized, high-quality clinical and laboratory data including genotyping, phenotyping, and documentation of environmental exposures and promote an integrated and collaborative community across the UDN and among laboratory and clinical investigators focused on defining the pathophysiology, cell biologic, and molecular mechanisms that cause these difficult to diagnose diseases. Thirdly, the WUSM UDN Clinical Site will propose a bioinformatics plan for leveraging institutional infrastructure and expertise to develop innovative strategies to improve discovery of pathogenic variants. Fourthly, the assessment, dissemination, outreach, and training plan will accelerate assessment and dissemination of data, protocols, consent materials, and methods, availability of educational and outreach materials for participants, clinicians, and other researchers, engagement of underrepresented minorities, and training for students, fellows, staff, and faculty in collaboration with WUSM’s Clinical and Translational Science Award infrastructure. Finally, WUSM will make a clear institutional commitment to maintain its Clinical Site, to adapt UDN Phase I practices for sustainability, to contribute to formation of a sustainable national UDN resource, and to adapt to unique needs and unexpected circumstances that may arise once Common Fund support ends in fiscal year 2022.