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（Baylor College of Medicine）的行政补充2 疾病网络（UDN）临床网站（CS）。在UDN CS的第1 - 8年，我们为患者提供了 未诊断疾病（UDD）获得最先进的诊断方法，加速发现 诊断和管理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UDN和更广泛的 分享最佳实践和技术创新。我们一直是领先的校外 (non美国国立卫生研究院（NIH UDP）研究中心的患者接受率和亲自评估完成率，实现了100%的目标， 这两个项目的重要里程碑。在迄今已完成亲自评估的个案中， 在强有力的候选人中，解决率达到36%，另外还有12%。我们系统地实施了 对成纤维细胞进行RNA测序，以补充外显子组和基因组测序。我们做到这一点， 利用分子与人类遗传学系内的综合遗传学项目 （DMHG）。我们建议在第二个"延长费用"项目的第九年完成第一至第八年的工作， 这一提议得到了行政补充的支持。这包括完成临床评价， 受试者在2022年7月1日之前累积。我们预计，我们将接受额外的10个科目，并有 到第9年年底（2022年6月30日）完成对另外10个项目的评估。具体目标是：1）审查， 招募并评估UDN协调中心推荐的10名新受试者，作为正在进行的NIH UDN的一部分 议定书2)将此UDN工作流程整合到更广泛的特定于BCM的UDN可持续性计划中， 建立一个精简的标准操作程序，为未确诊的疾病中心（UDC）在华盛顿特区。第三章 通过利用现有的医疗保险，优先考虑未投保/未投保和代表性不足的人口， 项目的重点是推荐和招聘。

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

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

Missed diagnoses: Clinically relevant lessons learned through medical mysteries solved by the Undiagnosed Diseases Network.

• DOI: 10.1002/mgg3.1397
• 发表时间: 2020-10
• 期刊: Molecular genetics & genomic medicine
• 影响因子: 2
• 作者: Cope H;Spillmann R;Rosenfeld JA;Brokamp E;Signer R;Schoch K;Glanton E;Sullivan JA;Macnamara E;Lincoln S;Golden-Grant K;Undiagnosed Diseases Network;Orengo JP;Clark G;Burrage LC;Posey JE;Punetha J;Robertson A;Cogan J;Phillips JA 3rd;Martinez-Agosto J;Shashi V
• 通讯作者: Shashi V