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

未确诊疾病网络 (UDN) II 期 BCM 临床站点 (U01)

• 批准号: 10677141
• 负责人: Carlos A. Bacino
• 金额: $ 3.11万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10677141
• 关键词: Administrative Supplement; Area; Biological; Charge; Clinical; Clinical Medicine; Clinical Research; Communities; Complement; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Enrollment; Etiology; Evaluation; Evaluation Research; Extramural Activities; Fibroblasts; Funding; Genetic; Genomic medicine; Hispanic; Historically Black Colleges and Universities; Human Genetics; Human Resources; Hybrids; Institution; Medicine; Modeling; Molecular Genetics; National Center for Advancing Translational Sciences; National Human Genome Research Institute; Network-based; Participant; Pathway interactions; Patient Recruitments; Patients; Persons; Phase; Phenotype; Population; Procedures; Process; Protocols documentation; Provider; Research; Resources; Site; Technology; Testing; Texas; Underrepresented Populations; Uninsured; United States National Institutes of Health; Work; clinical care; clinical research site; college; cost; exome sequencing; genetic variant; genome sequencing; improved; innovation; multiple omics; programs; recruit; research clinical testing; standard of care; success; transcriptome sequencing; virtual platform

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.

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）临床部位（CS）。在UDN CS的1 - 8年中，我们为患者提供了 未诊断的疾病（UDD）访问最先进的诊断方法，加速发现 诊断和管理疾病中鉴定出的遗传变异的UDD，阐明的生物学机制 因果关系，导致改进治疗的潜在途径，并积极参与UDN和更广泛的途径 社区分享最佳实践和技术创新。我们一直是领先的室外 （非NIH UDP）在患者接受和人身评估完成中的站点，实现了100％的目标 该计划的这两个关键里程碑。在迄今已完成面对面评估的案件中，我们有 以强大的候选人的身份获得了36％的求解率。我们已经实施了系统 成纤维细胞上的RNA测序以补充外显子组和基因组测序。我们通过 利用分子和人类遗传学系中的综合遗传学计划 （DMHG）。我们建议在第二个“带有成本延期”的第9年完成年度1-8工作。 得到该建议的行政补充的支持。这包括完成的临床评估 2022年7月1日之前收到的受试者。我们预测我们将接受另外10个主题，并拥有 在9年底（2022年6月30日）之前完成了10次额外评估。具体目的是：1）审查， 招募并评估UDN协调中心提到的10个新主题，作为正在进行的NIH UDN的一部分 协议。 2）将此UDN工作流程整合到更广泛的BCM特定UDN可持续性计划中 在BCM上建立一个简化的标准疾病中心（UDC）的标准操作程序。 3） 通过利用现有 具有相同重点进行推荐和招聘的程序。

项目成果

What Has the Undiagnosed Diseases Network Taught Us About the Clinical Applications of Genomic Testing?

关于基因组检测的临床应用，未确诊疾病网络教会了我们什么？

• DOI: 10.1146/annurev-med-042120-014904
• 发表时间: 2022
• 期刊: Annual review of medicine
• 影响因子: 10.5
• 作者: Murdock,DavidR;Rosenfeld,JillA;Lee,Brendan
• 通讯作者: Lee,Brendan

De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures.

• DOI: 10.1186/s13229-021-00473-3
• 发表时间: 2021-10-26
• 期刊: Molecular autism
• 影响因子: 6.2
• 作者: Royer-Bertrand B;Jequier Gygax M;Cisarova K;Rosenfeld JA;Bassetti JA;Moldovan O;O'Heir E;Burrage LC;Allen J;Emrick LT;Eastman E;Kumps C;Abbas S;Van Winckel G;Undiagnosed Diseases Network;Chabane N;Zackai EH;Lebon S;Keena B;Bhoj EJ;Umair M;Li D;Donald KA;Superti-Furga A
• 通讯作者: Superti-Furga A

A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development.

• DOI: 10.1093/hmg/ddw390
• 发表时间: 2016-12-01
• 期刊: Human molecular genetics
• 影响因子: 3.5
• 作者: Bashamboo A;Donohoue PA;Vilain E;Rojo S;Calvel P;Seneviratne SN;Buonocore F;Barseghyan H;Bingham N;Rosenfeld JA;Mulukutla SN;Jain M;Burrage L;Dhar S;Balasubramanyam A;Lee B;Members of UDN;Dumargne MC;Eozenou C;Suntharalingham JP;de Silva K;Lin L;Bignon-Topalovic J;Poulat F;Lagos CF;McElreavey K;Achermann JC
• 通讯作者: Achermann JC

Phenotypic and genetic spectrum of ATP6V1A encephalopathy: a disorder of lysosomal homeostasis

• DOI: 10.1093/brain/awac145
• 发表时间: 2022-06-08
• 期刊: BRAIN
• 影响因子: 14.5
• 作者: Guerrini, Renzof;Mei, Davide;Fassio, Anna
• 通讯作者: Fassio, Anna

A dominant negative variant of RAB5B disrupts maturation of surfactant protein B and surfactant protein C.

• DOI: 10.1073/pnas.2105228119
• 发表时间: 2022-02-08
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Huang H;Pan J;Spielberg DR;Hanchard NA;Scott DA;Burrage LC;Dai H;Murdock D;Rosenfeld JA;Mohammad A;Huang T;Lindsey AG;Kim H;Chen J;Ramu A;Morrison SA;Dawson ZD;Hu AZ;Tycksen E;Silverman GA;Baldridge D;Wambach JA;Undiagnosed Diseases Network;Pak SC;Brody SL;Schedl T
• 通讯作者: Schedl T