title: The usefulness of whole-exome sequencing in routine clinical practice.
abstract: OBJECTIVE
  Reports of the use of whole-exome sequencing in clinical practice are limited. We report our experience with whole-exome sequencing in 115 patients in a single center and evaluate its feasibility and clinical usefulness in clinical care.
  
  
  METHODS
  Whole-exome sequencing was utilized based on the judgment of three clinical geneticists. We describe age, gender, ethnicity, consanguinity, indication for testing, family history, insurance, laboratory results, clinician interpretation of results, and impact on patient care.
  
  
  RESULTS
  Most patients were children (78.9%). The most common indications for testing were birth defects (24.3%) and developmental delay (25.2%). We identified four new candidate human disease genes and possibly expanded the disease phenotypes associated with five different genes. Establishing a diagnosis led to discontinuation of additional planned testing in all patients, screening for additional manifestations in eight, altered management in fourteen, novel therapy in two, identification of other familial mutation carriers in five, and reproductive planning in six.
  
  
  CONCLUSIONS
  Our results show that whole-exome sequencing is feasible, has clinical usefulness, and allows timely medical interventions, informed reproductive choices, and avoidance of additional testing. Our results also suggest phenotype expansion and identification of new candidate disease genes that would have been impossible to diagnose by other targeted testing methods.
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, New York, New York, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Iglesias
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, New York, New York, USA.
authors.forename: Kwame
authors.initials: K
authors.lastname: Anyane-Yeboa
authors.affiliation: Division of Molecular Genetics, Department of Pediatrics, Columbia University Medical Center, New York, New York, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Wynn
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, New York Presbyterian Hospital, New York, New York, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Wilson
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, New York Presbyterian Hospital, New York, New York, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Truitt Cho
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, New York Presbyterian Hospital, New York, New York, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: Guzman
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, New York Presbyterian Hospital, New York, New York, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sisson
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, New York Presbyterian Hospital, New York, New York, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Egan
authors.affiliation: 1] Division of Molecular Genetics, Department of Pediatrics, Columbia University Medical Center, New York, New York, USA [2] Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis / Q000379:methods*; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D059472:Exome; D005260:Female; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D015203:Reproducibility of Results; D012189:Retrospective Studies; D055815:Young Adult