Washington University School of Medicine Undiagnosed Diseases Network Clinical Site

1.0项目摘要 这一申请的科学前提是，个性化的翻译研究过程， 在第一阶段开发的未诊断疾病网络（UDN）是可扩展的，它对患者的影响， 通过在华盛顿增设一个临床研究中心， 大学医学院（WUSM）。WUSM代表一个大型学术医疗中心， 与世界知名的基础科学能力相结合，并在基因优先方法方面展示了专业知识 为患有未确诊疾病的患者。高度合作的临床和生物医学研究文化， WUSM促进部门内和跨部门的互动，与机构基因组，临床，计算， 和模型系统专家，并与同事在区域，国家和国际。这些相互作用 支持儿科和成人患者的招募、选择、评估、诊断发现和随访， 通过既有的网络和个人转诊来治疗未确诊的疾病。在这个基础设施的基础上， WUSM的教职员工将推进UDN在诊断和管理疾病方面的成功， 未确诊的患者，首先，使用，完善和改进在第一阶段设计的协议， UDN用于每年对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，并促进一个综合和 UDN以及实验室和临床研究者之间的协作社区，重点关注 定义导致这些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临床研究中心将提出一项生物信息学计划， 基础设施和专业知识，以制定创新战略，以改善致病性变异的发现。 第四，评估、传播、外联和培训计划将加快评估和 传播数据、方案、同意材料和方法，提供教育和外联 为参与者、临床医生和其他研究人员提供的材料，代表性不足的少数群体的参与，以及 与WUSM的临床和转化科学合作，为学生，研究员，工作人员和教师提供培训 奖励基础设施。最后，WUSM将作出明确的机构承诺，以维持其临床 网站，以适应UDN第一阶段的可持续性做法，以促进形成一个可持续的国家 UDN资源，并适应独特的需求和意外的情况下，可能会出现一次 共同基金支持将于2022财年结束。

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.