Tifft Cynthia J, Adams David R
aNIH Undiagnosed Diseases Program, Office of the Director, NIH Common Fund bOffice of the Clinical Director and Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Curr Opin Pediatr. 2014 Dec;26(6):626-33. doi: 10.1097/MOP.0000000000000155.
To review the approach to undiagnosed patients and results of the National Institutes of Health (NIH) undiagnosed diseases program (UDP), and discuss its benefits to patients, academic medical centers, and the greater scientific community.
The NIH UDP provides comprehensive and collaborative evaluations for patients with objective findings of disease whose diagnoses have long eluded the medical community. Intensive review of patient records, careful phenotyping, and new genomic technologies have resulted in the diagnosis of new and extremely rare conditions, expanded the phenotypes of rare disorders, and determined that symptoms are caused by more than one disorder in a family.
Many children and adults with complex phenotypes remain undiagnosed despite years of searching. The most common undiagnosed disorders involve a neurologic phenotype. Comprehensive phenotyping and genomic analysis utilizing nuclear families can provide a diagnosis in some cases and provide good 'lead' candidate genes for others. A UDP can be important for patients, academic medical centers, the scientific community, and society.
回顾针对未确诊患者的诊疗方法以及美国国立卫生研究院（NIH）未确诊疾病项目（UDP）的成果，并探讨该项目对患者、学术医疗中心及更广泛科学界的益处。
NIH的UDP为那些有客观疾病表现但长期以来诊断一直未被医学界明确的患者提供全面且协作性的评估。对患者记录的深入审查、细致的表型分析以及新的基因组技术，已促成了新的极其罕见病症的诊断，扩展了罕见疾病的表型，并确定在一个家庭中症状是由不止一种疾病引起的。
许多具有复杂表型的儿童和成人尽管经过多年排查仍未得到诊断。最常见的未确诊疾病涉及神经学表型。利用核心家庭进行全面的表型分析和基因组分析，在某些情况下可得出诊断结果，为其他情况提供良好的“潜在”候选基因。UDP对患者、学术医疗中心、科学界及社会都可能具有重要意义。
