TY - JOUR
T1 - The NIH Undiagnosed Diseases Program and Network
T2 - Applications to modern medicine
AU - Gahl, William A.
AU - Mulvihill, John J.
AU - Toro, Camilo
AU - Markello, Thomas C.
AU - Wise, Anastasia L.
AU - Ramoni, Rachel B.
AU - Adams, David R.
AU - Tifft, Cynthia J.
N1 - Funding Information:
We are deeply indebted to all the patients who entrusted their care to the UDP. The authors appreciate the technical assistance and advice of Jessica Albert, Manfred Boehm, Barbara Burton, Hannah Carlson-Donohoe, Michael Collins, Rachel Gafni, Fred Gill, Rena Godfrey, Gretchen Golas, Catherine Groden, Marjan Huizing, Michele Nehrebecky, Galina Nesterova, Tyler Pierson, Sergio Rosenzweig, Dimitre Simeonov, Stephen F. Traynelis, Zaheer Valivullah, Lynne Wolfe, Hongjie Yuan, Shira G. Ziegler, and the entire UDP staff. This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute and the NIH Common Fund , through the Office of Strategic Coordination, Office of the NIH Director. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2016
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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 Nine vignettes (two unpublished) illustrate the relevance of an undiagnosed diseases program to complex and common disorders, the coincidence of multiple rare single gene disorders in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.
AB - 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.
KW - Exome sequencing
KW - Interdisciplinary research
KW - Precision medicine
KW - Undiagnosed and rare diseases
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U2 - 10.1016/j.ymgme.2016.01.007
DO - 10.1016/j.ymgme.2016.01.007
M3 - Comment/debate
AN - SCOPUS:84956643608
VL - 117
SP - 393
EP - 400
JO - Biochemical Medicine and Metabolic Biology
JF - Biochemical Medicine and Metabolic Biology
SN - 1096-7192
IS - 4
ER -