@article{999,
  author = {Kimberly Splinter and David R. Adams and Carlos A. Bacino and Hugo J. Bellen and Jonathan A. Bernstein and Alys M. Cheatle-Jarvela and Christine M. Eng and Cecilia Esteves and William A. Gahl and Rizwan Hamid and Howard J. Jacob and Bijal Kikani and David M. Koeller and Isaac S. Kohane and Brendan H. Lee and Joseph Loscalzo and Xi Luo and Alexa T. McCray and Thomas O. Metz and John J. Mulvihill and Stanley F. Nelson and Christina G S Palmer and John A. Phillips and Leslie Pick and John H. Postlethwait and Chloe Reuter and Vandana Shashi and David A. Sweetser and Cynthia J. Tifft and Nicole M. Walley and Michael F. Wangler and Monte Westerfield and Matthew T. Wheeler and Anastasia L. Wise and Elizabeth A. Worthey and Shinya Yamamoto and Euan A. Ashley and Undiagnosed Diseases Network},
  title = {Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease.},
  abstract = {<p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.).</p>},
  year = {2018},
  journal = {New Engl J Med},
  volume = {379},
  pages = {2131-2139},
  month = {12/2018},
  issn = {1533-4406},
  doi = {10.1056/NEJMoa1714458},
  language = {eng},
}