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）：此RFA打算在未诊断的疾病网络（UDN）的一部分中建立临床部位，以便为未发现诊断诊断的患者提供进一步评估，但没有发现诊断。杜克大学的研究团队坚定地确定了这样的临床部位。以强大的合作为基础 两位主要研究人员，为未识别的遗传疾病患者建立了成功的基因组测序诊所。利用仔细的临床筛查，详细的表型，排除促成环境因素和拷贝数变体的排除；已经进行了整个外显子组测序，并且在大约50％的患者中已经确定了因果变异。因果变异已与患者的患者/家庭进行了传达，并为患者进行了进一步的医疗服务。除了具有基因组测序的经验外，我们还拥有罕见疾病的专家，作为调查团队的一部分，以及通过UDN提及的患者所必需的基础设施。这包括由小儿和成人专家组成的世界一流临床医生组成的多学科团队，他们将对患者进行深入的临床评估，并将参与有关遗传序列数据，数据分析和最终最终临床相关的研究与研究的讨论结论和杜克临床研究部门（DCRU）具有容纳医学关键患者的能力，并为所有必要的专家评估提供了临床氛围。我们的目标是：特定目标1：全面评估未诊断疾病的患者，利用我们中心的诊断专业范围，并选择有资格参加基因组测序的患者。特定目的2：分析基因组序列数据，以确定表型的因果变异和其他感兴趣的变异，利用我们在稀有的，孤立的遗传疾病中的突变鉴定中的经验。特定目的3：有效地传达结果并为患者及其家人提供遗传咨询，借助我们到目前为止获得的经验。特定目的4：评估患者对诊断基因组测序结果的期望和理解，并有助于开发共同方案，以在整个UDN进行评估。我们提案的一个创新方面是对患者和家庭对过程和结果的看法的评估。这种做法对于帮助开发UDN中常见实践的协议特别有用。凭借这一经验，研究和临床团队提出了框架，我们坚定地定位为罕见和未诊断疾病的临床部位，并且能够评估整个生命中的患者。