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Short answer
The Undiagnosed Diseases Network (UDN) is an NIH-funded research study that brings together clinical and research experts across the United States to evaluate people whose conditions remain undiagnosed after extensive prior work-up. It is a research network, not a treatment clinic, and a diagnosis is not guaranteed. This page explains how the network is built and how its case process works, as a model for multi-site rare-disease research. It is general information, not medical advice.
Definition and scope
The UDN extends the NIH Undiagnosed Diseases Program, which began in 2008 at the NIH Clinical Center. According to the network’s published design paper (PubMed Central, PMC5294757), the original network phase was funded with a five-year, US$120 million budget from the NIH Common Fund, with the National Human Genome Research Institute as lead administrator, and saw its first patient in September 2015. The program’s own site describes the UDN as an NIH-funded research study aiming to bring together clinical and research experts from across the United States.
Leadership and funding arrangements have changed since that first phase, so treat the design paper as a description of the original structure; current arrangements are on the official UDN site (undiagnosed.hms.harvard.edu).
How the network is organised
The design paper describes a hub-and-spoke research structure. For lab and research staff the useful part is how each component is separated by function.
| Component | Role described in the design paper |
|---|---|
| Coordinating Center | Based in the Department of Biomedical Informatics at Harvard Medical School (opened January 2014); runs the online application gateway and the shared protocols. |
| Clinical sites | Seven original sites: the NIH Clinical Center; Baylor College of Medicine; Duke (with Columbia); the Harvard hospitals (Boston Children’s, Brigham and Women’s, Massachusetts General); Stanford; UCLA; and Vanderbilt. Each site decides which applicants to evaluate. |
| DNA sequencing cores | Baylor and HudsonAlpha; exome or genome sequencing results are interpreted jointly by the core and the clinical site. |
| Metabolomics cores | Battelle Pacific Northwest National Laboratory and Oregon Health & Science University. |
| Model-organism screening | Baylor and the University of Oregon. |
| Central biorepository | Vanderbilt, alongside local storage at each site. |
How a case moves through the network
Program rules from the official apply page and the design paper (both read 2026-11-08):
- Application. Submitted online through the UDN Gateway. A provider recommendation letter is required: in English, signed, on letterhead, and not written by the patient or a relative. Medical records (English) are optional at first; a patient narrative, photos or video are optional.
- Routing and review. Applications are typically routed to the nearest clinical site; the site decides, and a network review committee advises.
- Timing. The apply page says a clinical site typically makes contact within one month, and that once all information has arrived the network typically takes 6 to 8 weeks to decide what type of evaluation to offer.
- Evaluation. The design paper describes about five inpatient days of coordinated evaluation. Phenotypes are recorded in Human Phenotype Ontology terms using PhenoTips, and samples are held in both local and central biorepositories.
- Outcome. In the NIH program that preceded the network, time from evaluation to diagnosis ranged from one week to four years, as reported in the design paper.
The design paper’s eligibility criteria, as published at the time, were extensive prior evaluation without a diagnosis that explains the objective findings; novel features suggesting an unrecognised disorder; or similarly affected relatives. Current criteria are on the official apply page.
Why the design matters for labs and research administrators
The network is a worked example of multi-site rare-disease research infrastructure. Three design choices recur in other consortia:
- One shared vocabulary for phenotypes. Human Phenotype Ontology terms captured in a common tool let sites describe patients consistently before any sequencing result exists.
- Specialised cores instead of per-site capability. Sequencing, metabolomics and model-organism work sit in a few cores, so the clinical sites send samples rather than each building the capability. See the CASRAI guide on core facility staff and authorship for how that service work is credited.
- A central biorepository plus local storage. Duplicate holdings support re-analysis later; consent scope governs what can be done with them, which is covered in biobank consent models.
For the sequencing methods the cores rely on, see NGS DNA sequencing. For where controlled-access genomic datasets are typically deposited in US-funded work, see dbGaP.
Common misunderstandings
Is the UDN a clinic that treats patients?
No. The program describes itself as a research study. Evaluation aims at a diagnosis; it is not an ongoing treatment service.
Does the UDN guarantee a diagnosis?
No. The design paper reports a wide range of time to diagnosis in its predecessor program, and acceptance and evaluation type are decided case by case.
Is the UDN the same as the NIH Undiagnosed Diseases Program?
No. The NIH program (from 2008, NIH Clinical Center) came first and is one site of the network, which extends it to multiple institutions.
Is the UDN the same as Undiagnosed Diseases Network International?
They are named similarly but should not be assumed to be the same organisation; check each programme’s own site for its scope and rules.
FAQ
How do I apply to the Undiagnosed Diseases Network?
Through the online UDN Gateway on the official apply page, with a required provider recommendation letter. Questions can go to the contact details listed on that page.
How long does the UDN take to respond?
The apply page states a clinical site typically makes contact within one month and the network typically takes 6 to 8 weeks to decide the type of evaluation once everything is received.
Who funds the UDN?
The original phase was a five-year NIH Common Fund programme with NHGRI as lead administrator, per the design paper.
Sources
- Undiagnosed Diseases Network design paper, PubMed Central PMC5294757, pmc.ncbi.nlm.nih.gov/articles/PMC5294757, read 2026-11-08.
- UDN, How to apply, undiagnosed.hms.harvard.edu/apply, read 2026-11-08.
- UDN home page, undiagnosed.hms.harvard.edu, read 2026-11-08.
