@article{5dc1e0c6e6b6466cb40cb7817a2c07e0,
title = "Clinical sites of the Undiagnosed Diseases Network: unique contributions to genomic medicine and science",
abstract = "Purpose: The NIH Undiagnosed Diseases Network (UDN) evaluates participants with disorders that have defied diagnosis, applying personalized clinical and genomic evaluations and innovative research. The clinical sites of the UDN are essential to advancing the UDN mission; this study assesses their contributions relative to standard clinical practices. Methods: We analyzed retrospective data from four UDN clinical sites, from July 2015 to September 2019, for diagnoses, new disease gene discoveries and the underlying investigative methods. Results: Of 791 evaluated individuals, 231 received 240 diagnoses and 17 new disease–gene associations were recognized. Straightforward diagnoses on UDN exome and genome sequencing occurred in 35% (84/240). We considered these tractable in standard clinical practice, although genome sequencing is not yet widely available clinically. The majority (156/240, 65%) required additional UDN-driven investigations, including 90 diagnoses that occurred after prior nondiagnostic exome sequencing and 45 diagnoses (19%) that were nongenetic. The UDN-driven investigations included complementary/supplementary phenotyping, innovative analyses of genomic variants, and collaborative science for functional assays and animal modeling. Conclusion: Investigations driven by the clinical sites identified diagnostic and research paradigms that surpass standard diagnostic processes. The new diagnoses, disease gene discoveries, and delineation of novel disorders represent a model for genomic medicine and science.",
keywords = "exome sequencing, genome sequencing, phenotyping, ultrarare diseases, undiagnosed diseases",
author = "{Undiagnosed Diseases Network} and Kelly Schoch and Cecilia Esteves and Anna Bican and Rebecca Spillmann and Heidi Cope and Allyn McConkie-Rosell and Nicole Walley and Liliana Fernandez and Kohler, {Jennefer N.} and Devon Bonner and Chloe Reuter and Nicholas Stong and Mulvihill, {John J.} and Donna Novacic and Lynne Wolfe and Ayat Abdelbaki and Camilo Toro and Cyndi Tifft and May Malicdan and William Gahl and Pengfei Liu and John Newman and Goldstein, {David B.} and Jason Hom and Jacinda Sampson and Wheeler, {Matthew T.} and Alejandro, {Mercedes E.} and Azamian, {Mahshid S.} and Bacino, {Carlos A.} and Ashok Balasubramanyam and Burrage, {Lindsay C.} and Chao, {Hsiao Tuan} and Clark, {Gary D.} and Craigen, {William J.} and Hongzheng Dai and Dhar, {Shweta U.} and Emrick, {Lisa T.} and Goldman, {Alica M.} and Hanchard, {Neil A.} and Fariha Jamal and Lefkothea Karaviti and Lalani, {Seema R.} and Lee, {Brendan H.} and Lewis, {Richard A.} and Ronit Marom and Surendra Dasari and Lanpher, {Brendan C.} and Lanza, {Ian R.} and Eva Morava and Devin Oglesbee",
note = "Funding Information: We thank all of the individuals and their families for their participation in this study. Research reported in this paper was supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director under award number(s) U01HG007672 (Duke University), U01HG007708 (Stanford Medicine), U01HG007674 (Vanderbilt University Medical Center), and U01HG007530 (Coordinating Center at Harvard Medical School). The NIH clinical site (UDP) was supported by the National Human Genome Research Institute (NHGRI) Intramural Research Program under award number HG000215-17. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2020, American College of Medical Genetics and Genomics.",
year = "2021",
month = feb,
doi = "10.1038/s41436-020-00984-z",
language = "English (US)",
volume = "23",
pages = "259--271",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "2",
}