title: Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability.
abstract: This study investigated whole-exome sequencing (WES) yield in a subset of intellectually disabled patients referred to our clinical diagnostic center and calculated the total costs of these patients' diagnostic trajectory in order to evaluate early WES implementation.
  
  
  
  We compared 17 patients' trio-WES yield with the retrospective costs of diagnostic procedures by comprehensively examining patient records and collecting resource use information for each patient, beginning with patient admittance and concluding with WES initiation. We calculated cost savings using scenario analyses to evaluate the costs replaced by WES when used as a first diagnostic tool.
  
  
  
  WES resulted in diagnostically useful outcomes in 29.4% of patients. The entire traditional diagnostic trajectory average cost was $16,409 per patient, substantially higher than the $3,972 trio-WES cost. WES resulted in average cost savings of $3,547 for genetic and metabolic investigations in diagnosed patients and $1,727 for genetic investigations in undiagnosed patients.
  
  
  
  The increased causal variant detection yield by WES and the relatively high costs of the entire traditional diagnostic trajectory suggest that early implementation of WES is a relevant and cost-efficient option in patient diagnostics. This information is crucial for centers considering implementation of WES and serves as input for future value-based research into diagnostics.Genet Med 18 9, 949-956.
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.|Center for Molecular Medicine, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Glen R
authors: 0000-0002-8653-2643
authors: GR
authors: Monroe
authors: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors: Gerardus W
authors: GW
authors: Frederix
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.|Center for Molecular Medicine, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Sanne M C
authors: 0000-0002-2054-5521
authors: SM
authors: Savelberg
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Tamar I
authors: 0000-0003-1402-281X
authors: TI
authors: de Vries
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.|Center for Molecular Medicine, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Karen J
authors: KJ
authors: Duran
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Jasper J
authors: JJ
authors: van der Smagt
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Paulien A
authors: PA
authors: Terhal
authors: Department of Metabolic Diseases, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors: Peter M
authors: PM
authors: van Hasselt
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Hester Y
authors: HY
authors: Kroes
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.|Center for Molecular Medicine, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Nanda M
authors: NM
authors: Verhoeven-Duif
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.|Center for Molecular Medicine, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Isaäc J
authors: IJ
authors: Nijman
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.|Center for Molecular Medicine, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Ellen C
authors: EC
authors: Carbo
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Koen L
authors: KL
authors: van Gassen
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.|Center for Molecular Medicine, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Nine V
authors: NV
authors: Knoers
authors: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors: Anke M
authors: AM
authors: Hövels
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Mieke M
authors: MM
authors: van Haelst
authors: Department of Metabolic Diseases, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors: Gepke
authors: G
authors: Visser
authors: Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.|Center for Molecular Medicine, Utrecht University Medical Center, Utrecht, The Netherlands.
authors: Gijs
authors: 0000-0003-3033-0329
authors: G
authors: van Haaften
mesh_terms: D003365:Costs and Cost Analysis; D059472:Exome; D005260:Female; D005820:Genetic Testing / Q000191:economics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000191:economics / Q000235:genetics; D008297:Male; D017422:Sequence Analysis, DNA; D000073359:Exome Sequencing / Q000191:economics / Q000379:methods*