An integrated and diverse genomic medicine program for undiagnosed diseases

针对未确诊疾病的综合且多样化的基因组医学计划

• 批准号: 9081624
• 负责人: David B. Goldstein
• 金额: $ 230万
• 依托单位: DUKE UNIVERSITY
• 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/9081624
• 关键词: Adult; Affect; Biological Assay; Caring; Childhood; Clinic; Clinical; Clinical Research; Collaborations; Copy Number Polymorphism; Country; Data; Data Analyses; Detection; Development; Diagnosis; Diagnostic; Disease; Emotional; Ensure; Environmental Risk Factor; Etiology; Evaluation; Exclusion; Family; Genetic; Genetic Counseling; Genetic screening method; Genome; Genomic medicine; Geography; Glycogen; Glycogen storage disease type II; Health; Health Care Costs; Health Policy; Health Sciences; Hereditary Disease; Housing; Human Resources; Individual; Inherited; Insurance Coverage; Knowledge; Laboratories; Longevity; Medical; Mission; Mutation; Online Mendelian Inheritance In Man; Outcome; Patient Care; Patient Selection; Patients; Perception; Personal Satisfaction; Phenotype; Positioning Attribute; Principal Investigator; Process; Protocols documentation; Publishing; Rare Diseases; Research; Research Infrastructure; Research Personnel; Running; Services; Site; Societies; Specialist; Test Result; Time; Universities; Variant; Work; base; clinical research site; data collection evaluation; data sharing; exome sequencing; experience; genome sequencing; glycosylation; improved; innovation; interest; medical specialties; meetings; multidisciplinary; next generation sequencing; patient expectation; planetary Atmosphere; programs; psychosocial; research clinical testing; screening

DESCRIPTION (provided by applicant): This RFA intends to establish clinical sites, as part of an undiagnosed diseases network (UDN), to provide further evaluation for patients that have been through the diagnostic odyssey with no diagnosis found. The research team at Duke is robustly positioned to establish such a clinical site. Building on the strong collaboration between the two principal investigators, a successful genome sequencing clinic has been established for patients with unidentified genetic disorders. Utilizing careful clinical screening, detailed phenotyping, exclusion of contributing environmental factors and copy number variants; whole exome sequencing has been performed and causal variants have been identified in approximately 50% of patients. The causal variants have been communicated to the patients/families with genetic counseling and further medical care for the patients has been arranged. In addition to experience with genome sequencing, we also have experts in rare disorders as part of the investigative team and the infrastructure essential to evaluate patients referred through the UDN. This includes a multidisciplinary team of world-class clinicians consisting of both pediatric and adult specialists who will be performing in-depth clinical evaluations of the patients and will take part in research- related discussions regarding clinical correlation of genetic sequence data, data analysis and final conclusions and the Duke Clinical Research Unit (DCRU) that has the capability to house medically-critical patients and provides a clinical atmosphere for all necessary specialist evaluations. Our aims are: Specific Aim 1: Comprehensively evaluate patients with undiagnosed diseases, capitalizing on our center's range of diagnostic specialties and select patients eligible for genome sequencing. Specific Aim 2: Analyze genome sequence data to identify causal variants and other variants of interest to the phenotypes, utilizing our experience in mutation identification in rare, isolated genetic disorders. Specific Aim 3: Effectively communicate results and provide genetic counseling to the patients and their families, drawing upon the experience we have gained thus far. Specific Aim 4: Assess the patients' expectations and understanding of the results of the diagnostic genome sequencing and assist in the development of common protocols to assess this across the UDN. An innovative aspect of our proposal is the assessments of patients and families' perceptions about the process and outcomes. This practice would be particularly useful to help develop protocols for common practices within the UDN. With the experience the research and clinical team has accrued and the framework proposed, we are strongly positioned to be a clinical site for rare and undiagnosed diseases, with the ability to evaluate patients across the life-span.

描述(由申请人提供)：本RFA打算建立临床站点，作为未诊断疾病网络(UDN)的一部分，为已通过诊断奥德赛但未发现诊断的患者提供进一步评估。杜克大学的研究团队在建立这样一个临床站点方面做得很好。以两国之间的强大合作为基础 在两位首席研究人员的帮助下，一个成功的基因组测序诊所已经为不明原因的遗传病患者建立。利用仔细的临床筛查、详细的表型鉴定、排除致病环境因素和拷贝数变异；已经进行了完整的外显子组测序，并在大约50%的患者中发现了因果变异。已通过遗传咨询向患者/家属传达了因果变异，并为患者安排了进一步的医疗护理。除了在基因组测序方面的经验外，我们还拥有罕见疾病方面的专家，作为调查团队的一部分，以及评估通过UDN转诊的患者所必需的基础设施。这包括一个由世界级临床医生组成的多学科团队，该团队由儿科和成人专家组成，他们将对患者进行深入的临床评估，并将参加与研究相关的讨论，讨论遗传序列数据、数据分析和最终结论的临床相关性，以及杜克临床研究单位(DCRU)，该单位有能力容纳医学危重患者，并为所有必要的专家评估提供临床氛围。我们的目标是：具体目标1：全面评估未确诊疾病的患者，利用我们中心的一系列诊断专业，选择符合基因组测序条件的患者。具体目标2：分析基因组序列数据，利用我们在罕见、孤立遗传疾病的突变鉴定方面的经验，识别因果变异和其他与表型相关的变异。具体目标3：借鉴我们迄今取得的经验，有效地沟通结果，并为患者及其家人提供遗传咨询。具体目标4：评估患者对诊断基因组测序结果的期望和了解，并协助制定通用方案，以评估整个UDN。我们建议的一个创新方面是对患者和家属对过程和结果的看法的评估。这一做法将特别有助于为统一域名系统内的常见做法制定协议。凭借研究和临床团队积累的经验以及提出的框架，我们有能力成为罕见和未诊断疾病的临床站点，有能力在整个生命周期内对患者进行评估。