BCM Clinical Site for an Undiagnosed Disease Network (UDN) Phase II (U01)

项目摘要 这是贝勒医学院(BCM)未诊断的行政补充2 疾病网络(UDN)临床站点(CS)。在UDNCS的第1-8年，我们为患者提供 未诊断疾病(UDD)获得最先进的诊断方法，加速发现 诊断和处理UDD，阐明疾病中已识别的遗传变异的生物学机制 因果关系，导致改善治疗的潜在途径，并积极参与普遍肾病和更广泛的 社区共享最佳实践和技术创新。我们已经跻身于领先的校外 (非NIH UDP)站点接受患者并完成面对面评估，实现100%的目标 这是该计划的两个关键里程碑。到目前为止，在完成亲自评估的案例中，我们有 获得了36%的解决率，另外还有12%的有力候选人。我们已经实施了系统的 对成纤维细胞进行RNA测序以补充外显子组和基因组测序。我们通过以下方式实现了这一点 利用分子和人类遗传学系内的综合遗传学计划 (DMHG)。我们建议在第二年的第9年完成第1-8年的工作，并延长成本 由这一拟议的行政补编提供支助。这包括完成对 受试者在2022年7月1日之前应计。我们预计，我们将接受额外的10个科目，并有 在第9年年底(2022年6月30日)之前完成对另外10个项目的评估。具体目的是：1)复习， 招募和评估由统一数字网络协调中心推荐的10个新对象，作为正在进行的美国国立卫生研究院统一数字网络的一部分 协议。2)将此UDN工作流程集成到更广泛的BCM特定UDN可持续发展计划中，该计划将 为BCM的未诊断疾病中心(UDC)建立简化的标准操作程序。3) 利用现有资源，优先考虑未参保/未参保和代表不足的人群进行UDN评估 转介和招聘的重点相同的计划。

Project Summary This is an administrative supplement 2 for the Baylor College of Medicine (BCM) Undiagnosed Diseases Network (UDN) Clinical Site (CS). In years 1-8 of the UDN CS, we provided patients with undiagnosed diseases (UDD) access to state of the art diagnostic methods, accelerated discovery in diagnosing and managing UDD, elucidated biological mechanisms of identified genetic variants in disease causation, leading to potential pathways for improved treatments, and actively engaged the UDN and broader community to share best practices and technology innovations. We have been among the leading extramural (non NIH UDP) sites in patient acceptances and completion of in person evaluations, achieving 100% target for these two key milestones of the program. Of the cases with in-person evaluations completed to date, we have achieved a 36% solve rate with an additional 12% with strong candidates. We have implemented systematic RNA sequencing on fibroblasts to complement exome and genome sequencing. We have achieved this by leveraging an integrated genetics program housed within the Department of Molecular and Human Genetics (DMHG). We propose to complete years' 1-8 work in year 9 of this second “with cost extension” to be supported by this proposed administrative supplement. This includes completion of clinical evaluation of subjects accrued prior to July 1, 2022. We project that we will accept an additional 10 subjects and have completed evaluation of 10 additional by end of year 9 (June 30, 2022). The Specific Aims are to: 1) Review, recruit, and evaluate 10 new subjects referred by the UDN coordination center as part of the ongoing NIH UDN protocol. 2) Integrate this UDN workflow into the broader BCM-specific UDN sustainability plan which is to establish a streamlined standard operating procedure for the Undiagnosed Diseases Center (UDC) at BCM. 3) Prioritize under/uninsured and under-represented populations for UDN evaluation by leveraging existing programs with the same focus for referral and recruitment.