Format

Send to

Choose Destination
Mol Genet Metab. 2016 Apr;117(4):393-400. doi: 10.1016/j.ymgme.2016.01.007. Epub 2016 Jan 22.

The NIH Undiagnosed Diseases Program and Network: Applications to modern medicine.

Author information

1
NIH Undiagnosed Diseases Network, Common Fund, Office of the Director and the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States.
2
NIH Undiagnosed Diseases Network, Common Fund, Office of the Director and the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States; Department of Pediatrics, University of Oklahoma, Oklahoma City, OK, United States. Electronic address: John.Mulvihill@nih.gov.
3
Department for Biomedical Informatics, Harvard Medical School, Department of Oral Health Policy and Epidemiology, Harvard Dental School, Cambridge, MA, United States.

Abstract

INTRODUCTION:

The inability of some seriously and chronically ill individuals to receive a definitive diagnosis represents an unmet medical need. In 2008, the NIH Undiagnosed Diseases Program (UDP) was established to provide answers to patients with mysterious conditions that long eluded diagnosis and to advance medical knowledge. Patients admitted to the NIH UDP undergo a five-day hospitalization, facilitating highly collaborative clinical evaluations and a detailed, standardized documentation of the individual's phenotype. Bedside and bench investigations are tightly coupled. Genetic studies include commercially available testing, single nucleotide polymorphism microarray analysis, and family exomic sequencing studies. Selected gene variants are evaluated by collaborators using informatics, in vitro cell studies, and functional assays in model systems (fly, zebrafish, worm, or mouse).

INSIGHTS FROM THE UDP:

In seven years, the UDP received 2954 complete applications and evaluated 863 individuals. Nine vignettes (two unpublished) illustrate the relevance of an undiagnosed diseases program to complex and common disorders, the coincidence of multiple rare single gene disorders in individual patients, newly recognized mechanisms of disease, and the application of precision medicine to patient care.

CONCLUSIONS:

The UDP provides examples of the benefits expected to accrue with the recent launch of a national Undiagnosed Diseases Network (UDN). The UDN should accelerate rare disease diagnosis and new disease discovery, enhance the likelihood of diagnosing known diseases in patients with uncommon phenotypes, improve management strategies, and advance medical research.

KEYWORDS:

Exome sequencing; Interdisciplinary research; Precision medicine; Undiagnosed and rare diseases

PMID:
26846157
PMCID:
PMC5560125
DOI:
10.1016/j.ymgme.2016.01.007
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center