title: A genome sequencing program for novel undiagnosed diseases.
abstract: OBJECTIVE
  The Scripps Idiopathic Diseases of Man (IDIOM) study aims to discover novel gene-disease relationships and provide molecular genetic diagnosis and treatment guidance for individuals with novel diseases using genome sequencing integrated with clinical assessment and multidisciplinary case review. Here we describe the operational protocol and initial results of the IDIOM study.
  
  
  METHODS
  A total of 121 cases underwent first-tier review by the principal investigators to determine whether the primary inclusion criteria were satisfied, 59 (48.8%) underwent second-tier review by our clinician-scientist review panel, and 17 patients (14.0%) and their family members were enrolled.
  
  
  RESULTS
  60% of cases resulted in a plausible molecular diagnosis, and 18% of cases resulted in a confirmed molecular diagnosis. Two of three confirmed cases led to the identification of novel gene-disease relationships. In the third confirmed case a previously described but unrecognized disease was revealed. In all three confirmed cases a new clinical management strategy was initiated based on the genetic findings.
  
  
  CONCLUSIONS
  Genome sequencing provides tangible clinical benefit for individuals with idiopathic genetic disease, not only in the context of molecular genetic diagnosis of known rare conditions but also in cases where prior clinical information regarding a new genetic disorder is lacking.
authors: Scripps Genomic Medicine, Scripps Health, San Diego, California, USA.
authors: Cinnamon S
authors: CS
authors: Bloss
authors: Cypher Genomics, Inc., San Diego, California, USA.
authors: Ashley A Scott-Van
authors: AA
authors: Zeeland
authors: Scripps Genomic Medicine, Scripps Health, San Diego, California, USA.
authors: Sarah E
authors: SE
authors: Topol
authors: Scripps Genomic Medicine, Scripps Health, San Diego, California, USA.
authors: Burcu F
authors: BF
authors: Darst
authors: Scripps Genomic Medicine, Scripps Health, San Diego, California, USA.
authors: Debra L
authors: DL
authors: Boeldt
authors: Scripps Genomic Medicine, Scripps Health, San Diego, California, USA.
authors: Galina A
authors: GA
authors: Erikson
authors: Division of Pathology, Scripps Clinic, San Diego, California, USA.
authors: Kelly J
authors: KJ
authors: Bethel
authors: Pediatrics, Scripps Health, San Diego, California, USA.
authors: Robert L
authors: RL
authors: Bjork
authors: Department of Neurosciences, University of California San Diego, San Diego, California, USA.|Department of Pediatrics, University of California San Diego, San Diego, California, USA.
authors: Jennifer R
authors: JR
authors: Friedman
authors: Division of Neurology, Scripps Clinic, San Diego, California, USA.
authors: Nelson
authors: N
authors: Hwynn
authors: Division of Internal Medicine, Scripps Clinic, San Diego, California, USA.
authors: Bradley A
authors: BA
authors: Patay
authors: Division of Gastroenterology/Hepatology, Scripps Clinic, San Diego, California, USA.
authors: Paul J
authors: PJ
authors: Pockros
authors: Scripps Genomic Medicine, Scripps Health, San Diego, California, USA.
authors: Erick R
authors: ER
authors: Scott
authors: Division of Allergy and Immunology, Scripps Clinic, San Diego, California, USA.
authors: Ronald A
authors: RA
authors: Simon
authors: Division of Rheumatology, Scripps Clinic, San Diego, California, USA.
authors: Gary W
authors: GW
authors: Williams
authors: Scripps Genomic Medicine, Scripps Health, San Diego, California, USA.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
authors: Nicholas J
authors: NJ
authors: Schork
authors: Scripps Genomic Medicine, Scripps Health, San Diego, California, USA.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.|Division of Cardiology, Scripps Clinic, San Diego, California, USA.
authors: Eric J
authors: http://orcid.org/0000-0002-1478-4729
authors: EJ
authors: Topol
authors: Scripps Genomic Medicine, Scripps Health, San Diego, California, USA.|Cypher Genomics, Inc., San Diego, California, USA.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.|Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
authors: Ali
authors: http://orcid.org/0000-0003-0232-8053
authors: A
authors: Torkamani
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000628:therapy; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D007223:Infant; D008297:Male; D057089:Pathology, Molecular; D035583:Rare Diseases / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D017422:Sequence Analysis, DNA; D055815:Young Adult