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: 8882497
• 负责人: Katrina M Dipple
• 金额: $ 165.05万
• 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 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8882497
• 关键词: Address; Affect; Basic Science; Biochemical; Bioinformatics; Caring; Cellular biology; Clinic; Clinical; Clinical Management; Clinical Research; Clinical Sciences; Communication; Complex; Consent; County; DNA; Data; Data Collection; Development; Diagnosis; Diagnostic; Disclosure; Disease; Disease Management; Elements; Ensure; Etiology; Family; Family member; Foundations; Genes; Genetic; Genetic Counseling; Genome; Genomics; Goals; Health; Health Personnel; Healthcare; Healthcare Systems; Hereditary Disease; Human Genome; Individual; Institutes; Investigation; Laboratories; Link; Los Angeles; Medical Genetics; Medicine; Modeling; Mutation; Outcome; Patient Selection; Patients; Persons; Phenotype; Physicians; Population; Process; Rare Diseases; Recommendation; Registries; Reporting; Research; Research Infrastructure; Research Personnel; Resources; Site; Source; Standardization; Symptoms; System; Systems Analysis; Taxes; Technology; Testing; Time; Translating; Translational Research; Translations; Underinsured; United States; Variant; Visit; Work; base; clinical care; clinical investigation; clinical phenotype; clinical practice; clinical research site; clinically relevant; design; exome; exome sequencing; experience; follow-up; gene function; genetic variant; health care delivery; improved; medical specialties; methylome; network models; new technology; non-genomic; patient registry; psychosocial; rare variant; research clinical testing; socioeconomics

DESCRIPTION (provided by applicant): Undiagnosed diseases take a disproportionate toll on the health care system and on affected patients and families. Our proposal builds a collaborative network of researchers and healthcare providers, all with a stake in improving healthcare and outcomes for persons affected by various rare genetic disorders. Our approach will synergize basic and clinical research with the use of cutting-edge phenotyping technologies, an array of world class experts, and the translation of whole exome sequencing to the bedside. This will result in the development of a diagnostic process, rapidly translating clinical evidence into improved healthcare delivery. The Undiagnosed Disease Network (UDN) will provide the foundation to stimulate additional multi-and interdisciplinary basic, translational, and clinical research. 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. Our proposal delivers a platform for a UDN Clinical Site that functions locally and as part of a network to tackle the incorporation of genomic information into the clinical workflow, analyze patients' symptoms in a standardized and reproducible fashion, and perform research investigations to elucidate further the mechanisms of undiagnosed diseases. We will reach these overarching goals by implementing the following specific aims: Aim 1: Create 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 Our project integrates the resources of (1) the infrastructure of a Clinical and Translational Science Institute, allowing for a state-of-the-art clinical investigation of complex, multisystemic disorders, within a maximum of a week stay; (2) an experienced, team of clinicians from all specialty fields, that delivers clinical use of whole- exome sequencing, and it integration in the diagnostic process of rare, undiagnosed disorders; (3) the UCLA Clinical Genomic Center that offers bioinformatics data handling, and clinical laboratory exome sequencing, that will interpret and report clinically relevant DNA variants; (4) expertise in the investigation of environmental effects on clinical symptoms; (5) a registry infrastructure with longstanding experience in standardization of phenotypic and genotypic information; (6) access to a large, ethnically varied population and (7) a sustainable approach, with provisions to care for un/underinsured patients. Overall, our approach is designed to work cooperatively with the other Clinical Sites, the Coordinating Center, and the IRP-UDP, by capitalizing on our experiences in medical genetics, genetic counseling, clinical exome sequencing, and statistical genomics.

描述（由申请人提供）：未确诊的疾病对医疗保健系统以及受影响的患者和家庭造成不成比例的损失。我们的提案建立了一个由研究人员和医疗保健提供者组成的合作网络，所有这些都与改善受各种罕见遗传疾病影响的人的医疗保健和结果有关。我们的方法将通过使用尖端的表型分析技术，一系列世界级的专家，以及将整个外显子组测序转化到床边来协同基础和临床研究。这将导致诊断过程的发展，迅速将临床证据转化为改善的医疗服务。未诊断疾病网络（UDN）将为促进更多的多学科和跨学科基础，转化和临床研究提供基础。调查涉及多个系统的罕见疾病并将全面的基因组数据纳入临床护理带来了相当大的挑战，从大量遗传变异的解释到它们与症状的相关性，到与它们的披露相关的沟通问题，以及它们对临床管理的影响。我们的提案为UDN临床站点提供了一个平台，该平台在本地发挥作用，并作为网络的一部分，以解决将基因组信息纳入临床工作流程，以标准化和可重复的方式分析患者的症状，并进行研究调查，以进一步阐明未诊断疾病的机制。我们将通过实现以下具体目标来实现这些总体目标：目标1：创建一个在本地和网络范围内发挥作用的UDN临床模型目标2：研究新发和罕见疾病的临床表型目标3：研究新发和罕见疾病的潜在机制目标4：为新型和罕见疾病的转化研究建立一个网络范围的可持续基础设施我们的项目整合了（1）临床和转化科学研究所的基础设施，允许对复杂的， 多系统疾病，最多住院一周;（2）来自所有专业领域的经验丰富的临床医生团队，提供全外显子组测序的临床应用，并将其整合到罕见的未确诊疾病的诊断过程中;（3）加州大学洛杉矶分校临床基因组中心，提供生物信息学数据处理和临床实验室外显子组测序，解释和报告临床相关的DNA变异;（4）调查环境对临床症状影响的专业知识;（5）在表型和基因型信息标准化方面具有长期经验的注册基础设施;（6）接触到大量不同种族的人口;（7）可持续的方法，为没有保险/保险不足的病人提供护理。总体而言，我们的方法旨在与其他临床研究中心，协调中心和IRP-UDP合作，利用我们在医学遗传学，遗传咨询，临床外显子组测序和统计基因组学方面的经验。