Evidence map›Paper›PMID 42720004›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2026

Arriving at a diagnosis: Effective strategies used by the Undiagnosed Diseases Network.

Somin Hwang, Rachel M Brown, Dustin Baldridge, Erin E Baldwin, Alan H Beggs, Jonathan A Bernstein, Elizabeth Blue, Nicholas A Borja, Lorenzo D Botto, Lauren C Briere and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Somin HwangMGH Institute of Health Professions, Boston, MA; Harvard Medical School, Boston, MA. Electronic address: Somin_Hwang@dfci.harvard.edu.
Rachel M BrownHarvard Medical School, Boston, MA.
Dustin BaldridgeWashington University in St. Louis, St. Louis, MO.
Erin E BaldwinUniversity of Utah, Salt Lake City, UT.
Alan H BeggsBoston Children's Hospital, Boston, MA.
Jonathan A BernsteinStanford University School of Medicine, Stanford, CA.
Elizabeth BlueUniversity of Washington, Seattle, WA.
Nicholas A BorjaUniversity of Miami, Coral Gables, FL.
Lorenzo D BottoUniversity of Utah, Salt Lake City, UT.
Lauren C BriereMassachusetts General Hospital, Boston, MA.
Thomas CassiniVanderbilt University, Nashville, TN.
Cecilia EstevesHarvard Medical School, Boston, MA.
Elizabeth L FiegBrigham and Women's Hospital, Boston, MA.
Gail P JarvikUniversity of Washington, Seattle, WA.
Shilpa Nadimpalli KobrenHarvard Medical School, Boston, MA.
Mia P LevantoStanford University School of Medicine, Stanford, CA.
Julian A Martínez-AgostoUniversity of California, Los Angeles, Los Angeles, CA.
Shruti MarwahaStanford University School of Medicine, Stanford, CA.
Stanley F NelsonUniversity of California, Los Angeles, Los Angeles, CA.
Jill A RosenfeldBaylor College of Medicine, Houston, TX.
Tim SchedlWashington University in St. Louis, St. Louis, MO.
Tina K TruongBoston Children's Hospital, Boston, MA.
Jennifer A WambachWashington University in St. Louis, St. Louis, MO.
Matthew T WheelerStanford University School of Medicine, Stanford, CA.
Shinya YamamotoBaylor College of Medicine, Houston, TX; Texas Children's Hospital, Houston, TX.
Undiagnosed Diseases Network
Vandana ShashiDuke University, Durham, NC.
Alexa T McCrayHarvard Medical School, Boston, MA.
David R AdamsNational Institutes of Health, Bethesda, MD.
Kimberly LeBlancHarvard Medical School, Boston, MA. Electronic address: kimberly_leblanc@hms.harvard.edu.

Funding

Coordinating Center for the Undiagnosed Diseases NetworkU01HG007530 · NHGRI · HARVARD MEDICAL SCHOOL · PI KOHANE, ISAAC S. · 2014 to 2022
$30.2M
Pilot of New Technologies to Increase the Genomic Diagnosis of Undiagnosed Disease Network (UDN) PatientsU01HG007709 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI BACINO, CARLOS A., LEE, BRENDAN · 2014 to 2022
$14.3M
Vanderbilt Center for Undiagnosed Diseases (VCUD) - BiorepositoryU01HG007674 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COGAN, JOY D, HAMID, RIZWAN · 2014 to 2022
$13.7M
An integrated and diverse genomic medicine program for undiagnosed diseasesU01HG007672 · NHGRI · DUKE UNIVERSITY · PI SHASHI, VANDANA · 2014 to 2022
$13.4M
Center for Integrated Approaches to Undiagnosed DiseasesU01HG007690 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI LOSCALZO, JOSEPH · 2014 to 2022
$10.4M
Clinical Sequencing Core Facility for the Undiagnosed Diseases Network (UDN)U01HG007942 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI ENG, CHRISTINE · 2014 to 2021
$10.2M
UCLA clinical site for the investigation of undiagnosed disordersU01HG007703 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARTINEZ-AGOSTO, JULIAN, NELSON, STANLEY F. · 2014 to 2022
$10.1M
Zebrafish CoreU54NS093793 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI BELLEN, HUGO J · 2015 to 2022
$7.5M
What comes next? Engaging stakeholders in governance of participant data and relationships during the sunset of large genomic medicine research initiativesU01HG010218 · NHGRI · STANFORD UNIVERSITY · PI ASHLEY, EUAN A, BERNSTEIN, JONATHAN ADAM · 2018 to 2022
$6.3M
Pacific Northwest Undiagnosed Diseases Network Clinical SiteU01HG010233 · NHGRI · UNIVERSITY OF WASHINGTON · PI DIPPLE, KATRINA M, JARVIK, GAIL PAIRITZ · 2018 to 2022
$5.4M
WASHINGTON UNIVERSITY SCHOOL OF MEDICINE UNDIAGNOSED DISEASES NETWORK CLINICAL SITEU01HG010215 · NHGRI · WASHINGTON UNIVERSITY · PI DICKSON, PATRICIA I · 2018 to 2022
$3.4M
Washington University School of Medicine Undiagnosed Diseases Network Clinical SiteU01NS134354 · NINDS · WASHINGTON UNIVERSITY · PI PATRICIA I DICKSON · 2023 to 2026
$3.3M
NCATS NIH HHS U01 TR002471NHGRI NIH HHS F32 HG000130NHGRI NIH HHS U01 HG007530NHGRI NIH HHS U01 HG007672NHGRI NIH HHS U01 HG007674NHGRI NIH HHS U01 HG007690NHGRI NIH HHS U01 HG007703NHGRI NIH HHS U01 HG007709NHGRI NIH HHS U01 HG007942NHGRI NIH HHS U01 HG010215NHGRI NIH HHS U01 HG010217NHGRI NIH HHS U01 HG010218NHGRI NIH HHS U01 HG010219NHGRI NIH HHS U01 HG010230NHGRI NIH HHS U01 HG010233NINDS NIH HHS U01 NS134354NINDS NIH HHS U54 NS093793NINDS NIH HHS U54 NS108251
6 · The paper itself

Abstract

purposeDespite the increasing use of exome sequencing (ES) and genome sequencing (GS) in clinical settings, many individuals remain undiagnosed. This study examined the Undiagnosed Diseases Network (UDN)'s approach to establishing diagnoses for participants.

methodsAs a continuation of the first UDN cohort (9/16/2015-5/23/2017), this study reviewed diagnostic strategies and outcomes in the second UDN cohort (5/24/2017-6/30/2023).

resultsOver the study period, the proportion of UDN participants with prior ES/GS increased from 40.2% to 75.0%. The diagnostic rate for the UDN was 22.1% (379/1,713). Reanalysis/reinterpretation of sequencing data (prior ES: 21.4%, prior GS: 2.6%, UDN ES: 4.8%, UDN GS: 17.3%) yielded the greatest number of diagnoses, and the most frequent supporting strategy was case matching (25.6%). Aggregation of clinical information (57.7%) and clinical testing (42.3%) were the primary strategies used to identify non-genetic diagnoses (n=26). Notably, 235 diagnoses (59.9%) required research efforts beyond current standard clinical approaches.

conclusionThe UDN addresses challenging undiagnosed cases by integrating clinical expertise with research strategies that go beyond standard care. By employing these advanced approaches, the UDN resolves cases that remain unsolved in routine clinical settings, demonstrating the power of connecting research and clinical care.

Indexed as

Diagnostic strategiesexome sequencing (ES)genome sequencing (GS)rare diseaseresearch strategies

Identifiers

PMID42720004
PMCPMC13644579

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.