title: Diagnostic exome sequencing in 266 Dutch patients with visual impairment.
abstract: Inherited eye disorders have a large clinical and genetic heterogeneity, which makes genetic diagnosis cumbersome. An exome-sequencing approach was developed in which data analysis was divided into two steps: the vision gene panel and exome analysis. In the vision gene panel analysis, variants in genes known to cause inherited eye disorders were assessed for pathogenicity. If no causative variants were detected and when the patient consented, the entire exome data was analyzed. A total of 266 Dutch patients with different types of inherited eye disorders, including inherited retinal dystrophies, cataract, developmental eye disorders and optic atrophy, were investigated. In the vision gene panel analysis (likely), causative variants were detected in 49% and in the exome analysis in an additional 2% of the patients. The highest detection rate of (likely) causative variants was in patients with inherited retinal dystrophies, for instance a yield of 63% in patients with retinitis pigmentosa. In patients with developmental eye defects, cataract and optic atrophy, the detection rate was 50, 33 and 17%, respectively. An exome-sequencing approach enables a genetic diagnosis in patients with different types of inherited eye disorders using one test. The exome approach has the same detection rate as targeted panel sequencing tests, but offers a number of advantages. For instance, the vision gene panel can be frequently and easily updated with additional (novel) eye disorder genes. Determination of the genetic diagnosis improved the clinical diagnosis, regarding the assessment of the inheritance pattern as well as future disease perspective.
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute of Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Lonneke
authors.initials: L
authors.lastname: Haer-Wigman
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Wendy Ag
authors.initials: WA
authors.lastname: van Zelst-Stams
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute of Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Rolph
authors.initials: R
authors.lastname: Pfundt
authors.affiliation: Rotterdam Eye Hospital, Rotterdam, The Netherlands.
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Caroline Cw
authors.initials: CC
authors.lastname: Klaver
authors.affiliation: Department of Medical Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Joke Bgm
authors.initials: JB
authors.lastname: Verheij
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Breuning
authors.affiliation: Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Camiel Jf
authors.initials: CJ
authors.lastname: Boon
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: Kievit
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Virginie Jm
authors.initials: VJ
authors.lastname: Verhoeven
authors.affiliation: Department of Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jan Wr
authors.initials: JW
authors.lastname: Pott
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Suzanne Ceh
authors.initials: SC
authors.lastname: Sallevelt
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: van Hagen
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Astrid S
authors.initials: AS
authors.lastname: Plomp
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Hester Y
authors.initials: HY
authors.lastname: Kroes
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute of Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Lelieveld
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute of Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Jayne Y
authors.initials: JY
authors.lastname: Hehir-Kwa
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute of Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Steven
authors.initials: S
authors.lastname: Castelein
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute of Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Nelen
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute of Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Scheffer
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute of Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Dorien
authors.initials: D
authors.lastname: Lugtenberg
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute of Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Frans Pm
authors.initials: FP
authors.lastname: Cremers
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Lies
authors.initials: L
authors.lastname: Hoefsloot
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute of Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Helger G
authors.initials: HG
authors.lastname: Yntema
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D059472:Exome; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000473:pathology; D006801:Humans; D040582:Inheritance Patterns; D009426:Netherlands; D014786:Vision Disorders / Q000235:genetics* / Q000473:pathology