title: High Diagnostic Yield of Whole Exome Sequencing in Participants With Retinal Dystrophies in a Clinical Ophthalmology Setting.
abstract: OBJECTIVE
  To assess the diagnostic yield and the practicality of implementing whole exome sequencing within a clinical ophthalmology setting.
  
  
  METHODS
  Evaluation of a diagnostic protocol.
  
  
  METHODS
  setting: Patient participants were enrolled during clinical appointments in a university-based ophthalmic genetics clinic.
  
  
  METHODS
  Twenty-six patients with a variety of presumed hereditary retinal dystrophies.
  
  
  METHODS
  Participants were offered whole exome sequencing in addition to clinically available sequencing gene panels between July 2012 and January 2013 to determine the molecular etiology of their retinal dystrophy.
  
  
  METHODS
  Diagnostic yield and acceptability of whole exome sequencing in patients with retinal disorders.
  
  
  RESULTS
  Twenty-six of 29 eligible patients (∼90%) who were approached opted to undergo molecular testing. Each participant chose whole exome sequencing in addition to, or in lieu of, clinically available sequencing gene panels. Time to obtain informed consent was manageable in the clinical context. Whole exome sequencing successfully identified known pathogenic mutations or suspected deleterious variants in 57.7% of participants. Additionally, 1 participant had 2 autosomal dominant medically actionable incidental findings (unrelated to retinopathy) that were reported to enable the participant to take preventive action and reduce risk for future disease.
  
  
  CONCLUSIONS
  In this study, we identified the molecular etiology for more than half of all participants. Additionally, we found that participants were widely accepting of whole exome sequencing and the possibility of being informed about medically actionable incidental findings.
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: kristy_lee@med.unc.edu.
authors.forename: Kristy
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Berg
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Laura
authors.initials: L
authors.lastname: Milko
authors.affiliation: Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Kristy
authors.initials: K
authors.lastname: Crooks
authors.affiliation: Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.affiliation: The Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Chris
authors.initials: C
authors.lastname: Bizon
authors.affiliation: The Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Phillips
authors.initials: P
authors.lastname: Owen
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; The Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Wilhelmsen
authors.affiliation: Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Weck
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: James P
authors.initials: JP
authors.lastname: Evans
authors.affiliation: Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Seema
authors.initials: S
authors.lastname: Garg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004247:DNA / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009885:Ophthalmology / Q000379:methods*; D010375:Pedigree; D058499:Retinal Dystrophies / Q000175:diagnosis* / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D004247:DNA