The NIH Undiagnosed Diseases Program and Network

Applications to modern medicine

William A. Gahl, John J. Mulvihill, Camilo Toro, Thomas C. Markello, Anastasia L. Wise, Rachel B. Ramoni, David R. Adams, Cynthia J. Tifft

Research output: Contribution to journalArticle

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 Nine vignettes (two unpublished) illustrate the relevance of an undiagnosed diseases program to complex and common disorders, the coincidence of multiple rare single gene disorders in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.

Original languageEnglish (US)
JournalMolecular Genetics and Metabolism
DOIs
StateAccepted/In press - 2016

Fingerprint

Modern 1601-history
Medicine
Genes
Phenotype
Precision Medicine
Informatics
Zebrafish
Microarray Analysis
Rare Diseases
Diptera
Microarrays
Documentation
Polymorphism
Single Nucleotide Polymorphism
Biomedical Research
Patient Care
Hospitalization
Chronic Disease
Assays
Nucleotides

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Gahl, W. A., Mulvihill, J. J., Toro, C., Markello, T. C., Wise, A. L., Ramoni, R. B., ... Tifft, C. J. (Accepted/In press). The NIH Undiagnosed Diseases Program and Network: Applications to modern medicine. Molecular Genetics and Metabolism. https://doi.org/10.1016/j.ymgme.2016.01.007

The NIH Undiagnosed Diseases Program and Network : Applications to modern medicine. / Gahl, William A.; Mulvihill, John J.; Toro, Camilo; Markello, Thomas C.; Wise, Anastasia L.; Ramoni, Rachel B.; Adams, David R.; Tifft, Cynthia J.

In: Molecular Genetics and Metabolism, 2016.

Research output: Contribution to journalArticle

Gahl, William A. ; Mulvihill, John J. ; Toro, Camilo ; Markello, Thomas C. ; Wise, Anastasia L. ; Ramoni, Rachel B. ; Adams, David R. ; Tifft, Cynthia J. / The NIH Undiagnosed Diseases Program and Network : Applications to modern medicine. In: Molecular Genetics and Metabolism. 2016.
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