Genetic DiseaseNCT02450851
Clinical and Genetic Evaluation of Individuals With Undiagnosed Disorders Through the Undiagnosed Diseases Network
An observational study of Genetic Disease, run by National Human Genome Research Institute (NHGRI) at 33 sites in United States.
Trial summary
Without an explanation for severe and sometimes life-threatening symptoms, patients and their families are left in a state of unknown. Many individuals find themselves being passed from physician to physician, undergoing countless and often repetitive tests in the hopes of finding answers and insight about what the… Read more about this study
- Who is it for?
- Ages 1 month to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Genetic Disease
- How many people
- 20,000 participants
- Where
- 33 sitesUnited States
- Study dates
- 16 Sep 2015to 31 Dec 2099
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 100 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Individuals with undiagnosed conditions
Who may be able to join
- Ideal participants for tier 2-4 evaluations include individuals with:
- One or more objective findings pertinent to the phenotype for which a case was submitted.
- No diagnosis despite evaluation by specialists who assessed the patient for the objective finding(s).
- Agreement for the storage and sharing of information and biomaterials, in an identified fashion amongst the UDN centers, and in a de-identified fashion to research sites beyond the network.
- Participants unable to consent can be enrolled.
Who cannot join
- Individuals who are unlikely to be assigned to tier 2-4 evaluations include those with:
- Reported symptoms with no relevant objective findings.
- A diagnosis explaining objective findings.
- A diagnosis suggested on record review.
- Unwillingness to share data.
Trial locations and contacts
33 sites in 1 country. Contact the study team or a site near you to ask about taking part.
33 sites in 1 country
United States33 sites, 27 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Bruce Korf, M.D., bkorf@uab.edu
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
David Sweetser, M.D., 617-726-1742, dsweetser@partners.org
- Recruiting
Boston Children s Hospital
Boston, Massachusetts, 02115
Ingrid Holm, M.D., 617-919-2338, ingrid.holm@childrens.harvard.edu
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
David Sweetser, M.D., Ph.D., 617-726-1742, dsweetser@partners.org
- Completed
Harvard T.H. Chan School of Public Health
Boston, Massachusetts, 02115
- Not yet recruiting
Harvard U Faculty of Medicine
Boston, Massachusetts, 02115
Isaac Kohane, Not Listed, isaac_kohane@harvard.edu
- Not yet recruiting
Lurie Children s Hospital
Chicago, Illinois, 60611
Carlos Prada, M.D., 513-304-8906, cprada@luriechildrens.org
- Recruiting
Duke University Health System
Durham, North Carolina, 27710
Vandana Shashi, MD, Not Listed, Vandana.shashi@duke.edu
- Not yet recruiting
University of Oregon
Eugene, Oregon, 97403
Monte Westerfield, PhD, Not Listed, monte@uoneuro.uoregon.edu
- Recruiting
Baylor College of Medicine
Houston, Texas, 77030
Brendan Lee, M.D., 713-798-8835, blee@bcm.edu
- Completed
HudsonAlpha Institute for Biotechnology, Inc.
Huntsville, Alabama, 35806
- Recruiting
Indiana University
Indianapolis, Indiana, 46202-5262
Stephane Ware, M.D., 317-274-8938, stware@iu.edu
- Recruiting
University of California, Los Angeles
Los Angeles, California, 90095
Stanley Nelson, M.D., 310-794-7981, snelson@ucla.edu
- Recruiting
University of Miami Miller School of Medicine
Miami, Florida, 33136
Mustafa Tekin, MD, 305-243-2381, mtekin@med.miami.edu
- Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Rizwan Hamid, M.D., rizwan.hamid@vumc.org
- Active, not recruiting
New York Genome Center
New York, New York, 10013
- Recruiting
University of California, Irvine Medical Center
Orange, California, 92668
Changrui Xiao, M.D., 714-456-7720, changrx@hs.uci.edu
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104-6056
Daniel Rader, M.D., rader@pennmedicine.upenn.edu
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Kathleen Sullivan, M.D., Not Listed, sullivank@email.chop.edu
- Completed
Oregon Health Sciences University
Portland, Oregon, 97201-3098
- Completed
Pacific Northwest National Laboratory
Richland, Washington, 99354
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
Brendan Lanpher, lanpher.brendan@mayo.edu
- Recruiting
University of Utah
Salt Lake City, Utah, 84112
Lorenzo Botto, M.D., 801-581-8943, lorenzo.botto@hsc.utah.edu
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98101
Katrina Dipple, MD, PhD, Not Listed, katrina.dipple@seattlechildrens.org
- Recruiting
University of Washington
Seattle, Washington, 98195
Gail Jarvik, M.D., Not Listed, pair@uw.edu
- Recruiting
Washington University in St. Louis
St Louis, Missouri, 63110
Patricia Dickson, Not Listed, pdickson@wustl.edu
- Completed
Lucile Salter Packard Children's Hospital at Stanford
Stanford, California, 94020
- Recruiting
Stanford University
Stanford, California, 94305-5584
Euan Ashley, M.D., 650-736-1147, euan@stanford.edu
- Recruiting
Leland Stanford Junior University
Stanford, California, 94305
Euan Ashley, MD, PhD, Not Listed, euan@stanford.edu
- Recruiting
Stanford Hospital and Clinics
Stanford, California, 94305
Jonathan Bernstein, MD, PhD, Not Listed, jon.bernstein@stanford.edu
- Recruiting
Childrens National Medical Center
Washington D.C., District of Columbia, 20010
Eric Vilain, M.D., 202-476-3216, evilain@childrensnational.org
About this study
Official title: Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Without an explanation for severe and sometimes life-threatening symptoms, patients and their families are left in a state of unknown. Many individuals find themselves being passed from physician to physician, undergoing countless and often repetitive tests in the hopes of finding answers and insight about what the future may hold. This long and arduous journey to find a diagnosis does not end for many patients- the Office of Rare Diseases Research (ORDR) notes that 6% of individuals seeking their assistance have an undiagnosed disorder. In 2008, the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) was established with the goal of providing care and answers for these individuals with mysterious conditions who have long eluded diagnosis. The NIH UDP is a joint venture of the NIH ORDR, the National Human Genome Research Institute Intramural Research Program (NHGRI-IRP), and the NIH Clinical Research Center (CRC) (1-3). The goals of the NIH UDP are to: (1) provide answers for patients with undiagnosed diseases; (2) generate new knowledge about disease mechanisms; (3) assess the application of new approaches to phenotyping and the use of genomic technologies; and (4) identify potential therapeutic targets, if possible. To date, the UDP has evaluated 3300 medical records and admitted 750 individuals with rare and undiagnosed conditions to the NIH Clinical Center. The NIH UDP has identified more than 70 rare disease diagnoses and several new conditions. The success of the NIH UDP prompted the NIH Common Fund to support the establishment of a network of medical research centers, the Undiagnosed Diseases Network (UDN), for fiscal years 2013-2020. The clinical sites will perform extensive phenotyping, genetic analyses, and functional studies of potential disease-causing variants. The testing performed on patients involves medically indicated studies intended to help reach a diagnosis, as well as research investigations that include a skin biopsy, blood draws, and DNA analysis. In addition, the UDN will further the goals of the UDP by permitting the sharing of personally identifiable phenotypic and genotypic information within the network. By sharing participant information and encouraging collaboration, the UDN hopes to improve the understanding of rare conditions and advance the diagnostic process and care for individuals with undiagnosed diseases.
Read the detailed description
Without an explanation for severe and sometimes life-threatening symptoms, patients and their families are left in a state of unknown. Many individuals find themselves being passed from physician to physician, undergoing countless and often repetitive tests in the hopes of finding answers and insight about what the future may hold. This long and arduous journey to find a diagnosis does not end for many patients- the Office of Rare Diseases Research (ORDR) notes that 6% of individuals seeking their assistance have an undiagnosed disorder. In 2008, the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) was established with the goal of providing care and answers for these individuals with mysterious conditions who have long eluded diagnosis. The NIH UDP is a joint venture of the NIH ORDR, the National Human Genome Research Institute Intramural Research Program (NHGRI-IRP), and the NIH Clinical Research Center (CRC) (1-3). The goals of the NIH UDP are to: (1) provide answers for patients with undiagnosed diseases; (2) generate new knowledge about disease mechanisms; (3) assess the application of new approaches to phenotyping and the use of genomic technologies; and (4) identify potential therapeutic targets, if possible.1-3 Prior to formation of the Undiagnosed Diseases Network (UDN), the UDP had evaluated 3300 medical records, admitted 750 individuals with rare and undiagnosed conditions to the NIH, and identified more than 70 rare disease diagnoses and several new conditions. The success of the NIH UDP prompted the NIH Common Fund to support the establishment of a network of medical research centers, the UDN, for fiscal years 2013-2022. The clinical sites perform extensive phenotyping, genetic analyses, and functional studies of potential disease-causing variants. The testing performed on patients involves medically indicated studies intended to help reach a diagnosis, as well as research investigations that include a skin biopsy, blood draws, and DNA analysis. In addition, the UDN is furthering the goals of the UDP by permitting the sharing of personally identifiable phenotypic and genotypic information within the network. By sharing participant information and encouraging collaboration, the UDN hopes to improve the understanding of rare conditions and advance the diagnostic process and care for individuals with undiagnosed diseases.
- Conditions
- Genetic Disease
- Keywords
- Rare Diseases, Undiagnosed Diseases, Natural History
- Medical subject headings
- Genetic Diseases, Inborn, Rare Diseases, Undiagnosed Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Undiagnosed disorders | Patients with rare, undiagnosed disorders. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Create an integrated and collaborative research community across multiple clinical sites and between laboratory and clinical investigators prepared to investigate the pathophysiology of these new and rare diseases, the impact of the diagnostic p...
Create an integrated and collaborative research community across multiple clinical sites and between laboratory and clinical investigators prepared to investigate the pathophysiology of these new and rare diseases, the impact of the diagnostic process on patients and families, and share this understanding to identify improved options for optimal patient management.
Measured: Day 1-5 and followup
Facilitate research into the etiology of undiagnosed diseases, by collecting and sharing standardized, high-quality clinical and laboratory data including genotyping, phenotyping, and documentation of environmental exposures
Facilitate research into the etiology of undiagnosed diseases, by collecting and sharing standardized, high-quality clinical and laboratory data including genotyping, phenotyping, and documentation of environmental exposures.
Measured: Day 1-5 and followup
Improve the level of diagnosis and care for patients with undiagnosed diseases through the development of common and site-specific protocols designed by an enlarged community of investigators
Improve the level of diagnosis and care for patients with undiagnosed diseases through the development of common and site-specific protocols designed by an enlarged community of investigators.
Measured: Day 1-5 and followup
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2015 (estimated)
- Study start16 Sep 2015
- Primary completion16 Sep 2099 (estimated)
- Study completion31 Dec 2099 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (253)Papers the sponsor has linked to this study.
- Other trials for Genetic DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 20,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- William A Gahl, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02450851
- Sponsor's protocol ID
- 150130
- Other IDs
- 15-HG-0130
- Status last verified
- 14 Oct 2026
- First submitted
- 19 May 2015
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Rodan LH, Qi W, Ducker GS, Demirbas D, Laine R, Yang E, Walker MA, Eichler F, Rabinowitz JD, Anselm I, Berry GT; Undiagnosed Diseases Network (UDN). 5,10-methenyltetrahydrofolate synthetase deficiency causes a neurometabolic disorder associated with microcephaly, epilepsy, and cerebral hypomyelination. Mol Genet Metab. 2018 Sep;125(1-2):118-126. doi: 10.1016/j.ymgme.2018.06.006. Epub 2018 Jun 15.
PubMed 30031689DeBalsi KL, Newman JH, Sommerville LJ, Phillips JA 3rd, Hamid R, Cogan J, Fessel JP, Evans AM, Undiagnosed Diseases Network; Undiagnosed Diseases Network; Kennedy AD. A Case Study of Dysfunctional Nicotinamide Metabolism in a 20-Year-Old Male. Metabolites. 2023 Mar 8;13(3):399. doi: 10.3390/metabo13030399.
PubMed 36984839Shashi V, Schoch K, Spillmann R, Cope H, Tan QK, Walley N, Pena L, McConkie-Rosell A, Jiang YH, Stong N, Need AC, Goldstein DB; Undiagnosed Diseases Network. A comprehensive iterative approach is highly effective in diagnosing individuals who are exome negative. Genet Med. 2019 Jan;21(1):161-172. doi: 10.1038/s41436-018-0044-2. Epub 2018 Jun 15.
PubMed 29907797Spillmann RC, Tan QK, Reuter C, Schoch K; Undiagnosed Diseases Network; Kohler J, Bonner D, Zastrow D, Alkelai A, Baugh E, Cope H, Marwaha S, Wheeler MT, Bernstein JA, Shashi V; Undiagnosed Diseases Network. A concurrent dual analysis of genomic data augments diagnoses: Experiences of 2 clinical sites in the Undiagnosed Diseases Network. Genet Med. 2023 Apr;25(4):100353. doi: 10.1016/j.gim.2022.12.001. Epub 2022 Dec 5.
PubMed 36481303Jangam SV, Briere LC, Jay KL, Andrews JC, Walker MA, Rodan LH, High FA; Undiagnosed Diseases Network; Yamamoto S, Sweetser DA, Wangler MF. A de novo missense variant in EZH1 associated with developmental delay exhibits functional deficits in Drosophila melanogaster. Genetics. 2023 Aug 9;224(4):iyad110. doi: 10.1093/genetics/iyad110.
PubMed 37314226Briere LC, Walker MA, High FA, Cooper C, Rogers CA, Callahan CJ, Ishimura R, Ichimura Y, Caruso PA, Sharma N, Brokamp E, Koziura ME, Mohammad SS, Dale RC, Riley LG; Undiagnosed Diseases Network; Phillips JA, Komatsu M, Sweetser DA. A description of novel variants and review of phenotypic spectrum in UBA5-related early epileptic encephalopathy. Cold Spring Harb Mol Case Stud. 2021 Jun 11;7(3):a005827. doi: 10.1101/mcs.a005827. Print 2021 Jun.
PubMed 33811063Huang H, Pan J, Spielberg DR, Hanchard NA, Scott DA, Burrage LC, Dai H, Murdock D, Rosenfeld JA, Mohammad A, Huang T, Lindsey AG, Kim H, Chen J, Ramu A, Morrison SA, Dawson ZD, Hu AZ, Tycksen E, Silverman GA, Baldridge D, Wambach JA; Undiagnosed Diseases Network; Pak SC, Brody SL, Schedl T. A dominant negative variant of RAB5B disrupts maturation of surfactant protein B and surfactant protein C. Proc Natl Acad Sci U S A. 2022 Feb 8;119(6):e2105228119. doi: 10.1073/pnas.2105228119.
PubMed 35121658Yan YL, Titus T, Desvignes T, BreMiller R, Batzel P, Sydes J, Farnsworth D, Dillon D, Wegner J, Phillips JB, Peirce J, Dowd J; Undiagnosed Diseases Network; Buck CL, Miller A, Westerfield M, Postlethwait JH. A fish with no sex: gonadal and adrenal functions partition between zebrafish NR5A1 co-orthologs. Genetics. 2021 Feb 9;217(2):iyaa030. doi: 10.1093/genetics/iyaa030.
PubMed 33724412Ganapathi M, Friocourt G, Gueguen N, Friederich MW, Le Gac G, Okur V, Loaec N, Ludwig T, Ka C, Tanji K, Marcorelles P, Theodorou E, Lignelli-Dipple A, Voisset C, Walker MA, Briere LC, Bourhis A, Blondel M, LeDuc C, Hagen J, Cooper C, Muraresku C, Ferec C, Garenne A, Lelez-Soquet S, Rogers CA, Shen Y, Strode DK, Bizargity P, Iglesias A, Goldstein A, High FA, Network UD, Sweetser DA, Ganetzky R, Van Hove JLK, Procaccio V, Le Marechal C, Chung WK. A homozygous splice variant in ATP5PO, disrupts mitochondrial complex V function and causes Leigh syndrome in two unrelated families. J Inherit Metab Dis. 2022 Sep;45(5):996-1012. doi: 10.1002/jimd.12526. Epub 2022 Jul 11.
PubMed 35621276Gumusderelioglu S, Resch L, Brock T; Undiagnosed Diseases Network; Luxton GWG, Cope H, Tan QK, Hopkins C, Starr DA. A humanized Caenorhabditis elegans model of hereditary spastic paraplegia-associated variants in KLC4. Dis Model Mech. 2023 Aug 1;16(8):dmm050076. doi: 10.1242/dmm.050076. Epub 2023 Aug 29.
PubMed 37565267Reuter CM, Brimble E, DeFilippo C, Dries AM; Undiagnosed Diseases Network; Enns GM, Ashley EA, Bernstein JA, Fisher PG, Wheeler MT. A New Approach to Rare Diseases of Children: The Undiagnosed Diseases Network. J Pediatr. 2018 May;196:291-297.e2. doi: 10.1016/j.jpeds.2017.12.029. Epub 2018 Jan 11. No abstract available.
PubMed 29331327Keehan L, Jiang MM, Li X, Marom R, Dai H, Murdock D, Liu P, Hunter JV, Heaney JD, Robak L, Emrick L, Lotze T, Blieden LS; Undiagnosed Diseases Network; Lewis RA, Levin AV, Capasso J, Craigen WJ, Rosenfeld JA, Lee B, Burrage LC. A novel de novo intronic variant in ITPR1 causes Gillespie syndrome. Am J Med Genet A. 2021 Aug;185(8):2315-2324. doi: 10.1002/ajmg.a.62232. Epub 2021 May 5.
PubMed 33949769Shankar SP, Grimsrud K, Lanoue L, Egense A, Willis B, Horberg J, AlAbdi L, Mayer K, Utkur K, Monaghan KG, Krier J, Stoler J, Alnemer M, Shankar PR, Schaffrath R, Alkuraya FS, Brinkmann U, Eriksson LA, Lloyd K, Rauen KA; Undiagnosed Diseases Network. A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder. Genet Med. 2022 Jul;24(7):1567-1582. doi: 10.1016/j.gim.2022.03.014. Epub 2022 Apr 28.
PubMed 35482014Merriweather A, Murdock DR, Rosenfeld JA, Dai H, Ketkar S, Emrick L, Nicholas S, Lewis RA; Undiagnosed Diseases Network; Bacino CA, Scott DA, Lee B, Sutton VR, Potocki L, Burrage LC. A novel, de novo intronic variant in POGZ causes White-Sutton syndrome. Am J Med Genet A. 2022 Jul;188(7):2198-2203. doi: 10.1002/ajmg.a.62747. Epub 2022 Apr 9.
PubMed 35396900Hom J, Marwaha S, Postolova A, Kittle J, Vasquez R, Davidson J, Kohler J, Dries A, Fernandez-Betancourt L, Majcherska M, Dearlove J, Raghavan S, Vogel H, Bernstein JA, Fisher P, Ashley E, Sampson J, Wheeler M; Undiagnosed Diseases Network. A Patient with Sjogren's Syndrome and Subsequent Diagnosis of Inclusion Body Myositis and Light-Chain Amyloidosis. J Gen Intern Med. 2019 Jun;34(6):1058-1062. doi: 10.1007/s11606-019-04931-w. Epub 2019 Mar 18.
PubMed 30887439