UCLA clinical site for the investigation of undiagnosed disorders

加州大学洛杉矶分校临床中心，用于调查未确诊疾病

• 批准号: 10677461
• 负责人: JULIAN ANTONIO MARTINEZ
• 金额: $ 19.23万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 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/10677461
• 关键词: Administrative Supplement; Adult; Affect; Area; Basic Science; Caring; Charge; Childhood; Clinic; Clinic Visits; Clinical; Clinical Data; Clinical Management; Clinical Research; Communication; Consent; Consumption; Data; Data Collection; Diagnosis; Diagnostic; Disclosure; Disease; Disease Management; Electronic Mail; Elements; Enrollment; Equilibrium; Evaluation; Family; Family member; Financial Hardship; Funding; Gastrointestinal Diseases; Genetic Medicine; Genomics; Goals; Health; Health Personnel; Health system; Healthcare Systems; Human Genome; Immunology; Individual; Infrastructure; Insurance; Investigation; Laboratories; Link; Medical Records; Methods; Modeling; Myopathy; Neurology; Outcome; Participant; Patient Recruitments; Patients; Persons; Phase; Phenotype; Policies; Preparation; Process; Protocols documentation; RNA; Rare Diseases; Research; Research Personnel; Review Committee; Standardization; Structure; Symptoms; Syndrome; System; Taxes; Technology; Telemedicine; Telephone; Testing; Time; Translational Research; Translations; Underinsured; United States National Institutes of Health; Update; Variant; care outcomes; clinical care; clinical diagnostics; clinical investigation; clinical phenotype; clinical research site; cost; exome sequencing; experience; flexibility; genetic variant; genome sequencing; genomic data; improved; interest; medical specialties; meetings; member; operation; programs; psychologic; rare genetic disorder; recruit; research clinical testing; screening; transcriptomics; whole genome

Project Summary / Abstract Undiagnosed diseases take a disproportionate toll on the health care system and on affected patients and families. This second Administrative Supplement for 08/05/22-06/30/23 for the UCLA Clinical Site of the UDN is specifically to support re-initiation of ongoing recruitment, case evaluations pre-acceptance, determination of acceptance, and enrollment/consenting of the affected individual and relevant family members as well as clinical evaluation using the sustainable clinic approach with data return and wrap-up for 15 new UDN participants. This proposal is organized relative to a concurrent administrative supplement without budgetary overlap. We are poised to restart enrollment by 09/01/22, and complete evaluations by 6/30/22. This funding will allow the UCLA clinical site to cover research related costs for new enrollees. Our sustainable clinic model at UCLA will use the administrative supplement to provide for some of the costs associated with basic and clinical data collection related to the new enrollments, and clinical evaluations will be billed to patient insurance. This results in an improved diagnostic process for undiagnosed diseases. Investigating rare diseases involving multiple systems and incorporating comprehensive genomic data into clinical care creates considerable challenges, from the interpretation of vast amounts of genetic variants to their relevance to the symptoms, to the communication issues linked to their disclosure, and to their impact on clinical management. The Second Administrative Supplement of the UCLA Clinical Site of the UDN will support the ongoing communications with applicants, review of medical records, case discussion, acceptance decisions and communications, case evaluation at UCLA by telemedicine or in person within UCLA Health clinics and with insurance billing and patient co-pay, with coverage of research structure and research testing from NIH funds including a combination of a previously approved Administrative Supplement, this second supplement request, and a carryforward request from prior year unobligated balance. We continue to reach these overarching goals by implementing the following specific aims: Aim 1: Implement a UDN clinic model that functions locally and network-wide; Aim 2: Investigate the clinical phenotypes of new and rare disorders; Aim 3: Investigate the underlying mechanisms of new and rare disorders; Aim 4: Build a network-wide sustainable infrastructure for translational research on new and rare disorders

项目总结/摘要 未经诊断的疾病对卫生保健系统和受影响的患者造成不成比例的损失， 家庭UDN的UCLA临床研究中心的第二份管理补充文件（2012年8月5日至2013年6月30日） 特别是支持重新启动正在进行的征聘、案件评估、预先接受、确定 受影响个人和相关家庭成员以及 使用可持续临床方法进行临床评价，并对15个新UDN进行数据返回和总结 参与者本建议是相对于一个并行的行政补充，没有预算 重叠我们准备在2022年9月1日之前重新开始入组，并在2022年6月30日之前完成评估。这笔资金 将允许加州大学洛杉矶分校的临床网站，以支付研究相关的费用，为新的入组者。我们的可持续诊所模式 在加州大学洛杉矶分校将使用行政补充，以提供与基本和 与新入组相关的临床数据收集和临床评价将向患者收费 保险这导致对未诊断疾病的改进的诊断过程。调查罕见 涉及多个系统的疾病，并将全面的基因组数据纳入临床护理， 相当大的挑战，从解释大量的遗传变异，以其相关性， 症状，与其披露相关的沟通问题，以及其对临床管理的影响。 UDN的UCLA临床研究中心的第二份行政补充文件将支持正在进行的 与申请人的沟通，病历审查，病例讨论，受理决定和 通过远程医疗或在UCLA健康诊所内亲自进行病例评估， 保险账单和患者共同支付，包括NIH基金的研究结构和研究测试 包括先前批准的行政补充申请、第二次补充申请、 以及从上一年未支配余额结转的请求。我们将继续实现这些总体目标 通过实现以下具体目标：目标1：实施一个UDN诊所模型， 网络范围内;目的2：研究新发和罕见疾病的临床表型;目的3：研究 新的和罕见的疾病的基本机制;目标4：建立一个网络范围的可持续基础设施， 新型和罕见疾病的转化研究

项目成果

Expansion of NEUROD2 phenotypes to include developmental delay without seizures.

• DOI: 10.1002/ajmg.a.62064
• 发表时间: 2021-04
• 期刊: American journal of medical genetics. Part A
• 作者: Mis EK;Sega AG;Signer RH;Cartwright T;Ji W;Martinez-Agosto JA;Nelson SF;Palmer CGS;Lee H;Mitzelfelt T;Konstantino M;Undiagnosed Diseases Network;Jeffries L;Khokha MK;Marco E;Martin MG;Lakhani SA
• 通讯作者: Lakhani SA

MPEG1/Perforin-2 Haploinsufficiency Associated Polymicrobial Skin Infections and Considerations for Interferon-γ Therapy.

• DOI: 10.3389/fimmu.2020.601584
• 发表时间: 2020
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Merselis LC;Jiang SY;Nelson SF;Lee H;Prabaker KK;Baker JL;Munson GP;Butte MJ
• 通讯作者: Butte MJ

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

An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.

• DOI: 10.1038/s41436-020-01027-3
• 发表时间: 2021-04
• 期刊: Genetics in medicine : official journal of the American College of Medical Genetics
• 作者: Ferdinandusse S;McWalter K;Te Brinke H;IJlst L;Mooijer PM;Ruiter JPN;van Lint AEM;Pras-Raves M;Wever E;Millan F;Guillen Sacoto MJ;Begtrup A;Tarnopolsky M;Brady L;Ladda RL;Sell SL;Nowak CB;Douglas J;Tian C;Ulm E;Perlman S;Drack AV;Chong K;Martin N;Brault J;Brokamp E;Toro C;Gahl WA;Macnamara EF;Wolfe L;Undiagnosed Diseases Network;Waisfisz Q;Zwijnenburg PJG;Ziegler A;Barth M;Smith R;Ellingwood S;Gaebler-Spira D;Bakhtiari S;Kruer MC;van Kampen AHC;Wanders RJA;Waterham HR;Cassiman D;Vaz FM
• 通讯作者: Vaz FM

Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain.

• DOI: 10.1038/s41436-021-01152-7
• 发表时间: 2021-08
• 期刊: Genetics in medicine : official journal of the American College of Medical Genetics
• 作者: Marbach F;Stoyanov G;Erger F;Stratakis CA;Settas N;London E;Rosenfeld JA;Torti E;Haldeman-Englert C;Sklirou E;Kessler E;Ceulemans S;Nelson SF;Martinez-Agosto JA;Palmer CGS;Signer RH;Undiagnosed Diseases Network;Andrews MV;Grange DK;Willaert R;Person R;Telegrafi A;Sievers A;Laugsch M;Theiß S;Cheng Y;Lichtarge O;Katsonis P;Stocco A;Schaaf CP
• 通讯作者: Schaaf CP