Stanford Center for Undiagnosed Diseases

描述（由申请人提供）：未诊断疾病网络（UDN）将通过增加未诊断疾病患者与国家领先的临床医生和科学家的接触，扩大NIH非常成功的未诊断疾病计划。通过在斯坦福大学（CUDS）建立未诊断疾病中心，斯坦福大学医学处于独特的地位，可以推进未诊断疾病项目的使命。我们提出了一个计划，将（1）促进及时，准确的诊断患有未确诊疾病的患者;（2）推进对疾病的潜在机制的研究;（3）促进UDN内外的合作与协作。在目标1中，协调中心转介的患者将通过一项方案进行评估，包括访视前视频咨询和遗传咨询，为期一周的访视，在此期间将收集表型，生化，基因组和环境数据，以及视频会议随访。将从患者和亲属中收集血液用于产生诱导性多能干细胞。一个全站点的诊断委员会将审查病例进展，并确定内部和外部专家进行现场或虚拟视频咨询。远程呈现的使用将使来自世界各地的特定罕见疾病专家能够进行“虚拟咨询”。目标2专注于基因组分析，将利用我们成熟的基因组解释管道，可能包括斯坦福大学的“临床级”基因组捕获和测序技术。去识别数据集将在网络站点之间共享，并与科学合作者共享，使用本地和协调中心计算基础设施。基因组数据将通过“表型相互作用图谱”与个体表型特征的结构化分析相结合进行分析，以缩小感兴趣的遗传变异的搜索空间。信息学委员会将审查数据分析的进展情况，并确定是否需要进一步调查，包括多组学数据收集和分析。目标3利用了斯坦福大学医院与大学实验室的步行距离共同定位，这将使未诊断疾病网络利用独特的斯坦福大学资源，如干细胞研究所和人类免疫监测中心。发病机制委员会将审查确定个别病例发病机制的进展情况，并确定探索个别变异因果关系的途径和专家。每个病例和疾病假设将在该中心的疾病分子机制每周会议上提出，会议将被记录下来，以便在网络内传播。工作文件将通过一个安全的门户网站每周与其他网站共享。

DESCRIPTION (provided by applicant): The Undiagnosed Diseases Network (UDN) will expand the highly successful Undiagnosed Diseases Program of the NIH by increasing access for patients with undiagnosed diseases to the nation's leading clinicians and scientists. Stanford Medicine is uniquely placed to advance the mission of the Undiagnosed Disease Program through the establishment of a Center for Undiagnosed Diseases at Stanford (CUDS). We propose a program that will (1) facilitate timely, accurate diagnosis of patients with undiagnosed diseases; (2) advance research into underlying mechanisms of disease; and (3) foster cooperation and collaboration both within and outside the UDN. In Aim 1, patients referred by the Coordinating Center will be evaluated through a protocol including pre-visit video consultation and genetic counseling, a week-long visit during which phenotypic, biochemical, genomic and environmental data will be collected and video conference follow up. Blood will be collected for generation of inducible pluripotent stem cells from patients and relatives. A site-wide Diagnosis Board will review case progress and identify internal and external experts for live or virtual video consultation. Use of a telepresence will enable 'virtual consultation' with experts in specific rare diseases from wherever they are across the world. Aim 2 is focused on genomic analysis that will take advantage of our mature pipeline for genome interpretation and may include Stanford's 'clinical grade' genome capture and sequencing technology. De-identified datasets will be shared across network sites, and with scientific collaborators, using both local and coordinating center computing infrastructure. Genomic data will be analyzed in concert with structured analysis of individual phenotypic characteristics via a "phenotype interaction map" to narrow the search space for genetic variants of interest. An Informatics Board will review progress on data analysis and determine the need for further investigation including multi-omics data collection and analysis. Aim 3 takes advantage of the walking distance co-localization of Stanford Hospitals with the University labs, which will allow the Undiagnosed Diseases Network to utilize unique Stanford resources such as the Stem Cell Institute and the Human Immune Monitoring Center. A Pathogenesis Board will review progress on determination of pathogenesis in individual cases and identify avenues and experts for exploration of causality of individual variants. Each case and disease hypothesis will be presented at the Center's Molecular Mechanisms of Disease weekly conference which will be recorded for dissemination within the network. Working documents will be shared with other sites on a weekly basis via a secure web portal.