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Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease.

Publication ,  Journal Article
Splinter, K; Adams, DR; Bacino, CA; Bellen, HJ; Bernstein, JA; Cheatle-Jarvela, AM; Eng, CM; Esteves, C; Gahl, WA; Hamid, R; Jacob, HJ; Luo, X ...
Published in: N Engl J Med
November 29, 2018

BACKGROUND: Many patients remain without a diagnosis despite extensive medical evaluation. The Undiagnosed Diseases Network (UDN) was established to apply a multidisciplinary model in the evaluation of the most challenging cases and to identify the biologic characteristics of newly discovered diseases. The UDN, which is funded by the National Institutes of Health, was formed in 2014 as a network of seven clinical sites, two sequencing cores, and a coordinating center. Later, a central biorepository, a metabolomics core, and a model organisms screening center were added. METHODS: We evaluated patients who were referred to the UDN over a period of 20 months. The patients were required to have an undiagnosed condition despite thorough evaluation by a health care provider. We determined the rate of diagnosis among patients who subsequently had a complete evaluation, and we observed the effect of diagnosis on medical care. RESULTS: A total of 1519 patients (53% female) were referred to the UDN, of whom 601 (40%) were accepted for evaluation. Of the accepted patients, 192 (32%) had previously undergone exome sequencing. Symptoms were neurologic in 40% of the applicants, musculoskeletal in 10%, immunologic in 7%, gastrointestinal in 7%, and rheumatologic in 6%. Of the 382 patients who had a complete evaluation, 132 received a diagnosis, yielding a rate of diagnosis of 35%. A total of 15 diagnoses (11%) were made by clinical review alone, and 98 (74%) were made by exome or genome sequencing. Of the diagnoses, 21% led to recommendations regarding changes in therapy, 37% led to changes in diagnostic testing, and 36% led to variant-specific genetic counseling. We defined 31 new syndromes. CONCLUSIONS: The UDN established a diagnosis in 132 of the 382 patients who had a complete evaluation, yielding a rate of diagnosis of 35%. (Funded by the National Institutes of Health Common Fund.).

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

November 29, 2018

Volume

379

Issue

22

Start / End Page

2131 / 2139

Location

United States

Related Subject Headings

  • United States
  • Syndrome
  • Sequence Analysis, DNA
  • Rare Diseases
  • National Institutes of Health (U.S.)
  • Models, Animal
  • Male
  • Humans
  • Health Care Costs
  • Genetic Testing
 

Citation

APA
Chicago
ICMJE
MLA
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Splinter, K., Adams, D. R., Bacino, C. A., Bellen, H. J., Bernstein, J. A., Cheatle-Jarvela, A. M., … Undiagnosed Diseases Network, . (2018). Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease. N Engl J Med, 379(22), 2131–2139. https://doi.org/10.1056/NEJMoa1714458
Splinter, Kimberly, David R. Adams, Carlos A. Bacino, Hugo J. Bellen, Jonathan A. Bernstein, Alys M. Cheatle-Jarvela, Christine M. Eng, et al. “Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease.N Engl J Med 379, no. 22 (November 29, 2018): 2131–39. https://doi.org/10.1056/NEJMoa1714458.
Splinter K, Adams DR, Bacino CA, Bellen HJ, Bernstein JA, Cheatle-Jarvela AM, et al. Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease. N Engl J Med. 2018 Nov 29;379(22):2131–9.
Splinter, Kimberly, et al. “Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease.N Engl J Med, vol. 379, no. 22, Nov. 2018, pp. 2131–39. Pubmed, doi:10.1056/NEJMoa1714458.
Splinter K, Adams DR, Bacino CA, Bellen HJ, Bernstein JA, Cheatle-Jarvela AM, Eng CM, Esteves C, Gahl WA, Hamid R, Jacob HJ, Kikani B, Koeller DM, Kohane IS, Lee BH, Loscalzo J, Luo X, McCray AT, Metz TO, Mulvihill JJ, Nelson SF, Palmer CGS, Phillips JA, Pick L, Postlethwait JH, Reuter C, Shashi V, Sweetser DA, Tifft CJ, Walley NM, Wangler MF, Westerfield M, Wheeler MT, Wise AL, Worthey EA, Yamamoto S, Ashley EA, Undiagnosed Diseases Network. Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease. N Engl J Med. 2018 Nov 29;379(22):2131–2139.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

November 29, 2018

Volume

379

Issue

22

Start / End Page

2131 / 2139

Location

United States

Related Subject Headings

  • United States
  • Syndrome
  • Sequence Analysis, DNA
  • Rare Diseases
  • National Institutes of Health (U.S.)
  • Models, Animal
  • Male
  • Humans
  • Health Care Costs
  • Genetic Testing