Diagnostic exome sequencing in 266 Dutch patients with visual impairment

Lonneke Haer-Wigman, Wendy Ag van Zelst-Stams, Rolph Pfundt, L. Ingeborgh van den Born, Caroline Cw Klaver, Joke Bgm Verheij, Carel B. Hoyng, Martijn H. Breuning, Camiel Jf Boon, Anneke J. Kievit, Virginie Jm Verhoeven, Jan Wr Pott, Suzanne Ceh Sallevelt, Johanna M. van Hagen, Astrid S. Plomp, Hester Y. Kroes, Stefan H. Lelieveld, Jayne Y. Hehir-Kwa, Steven Castelein, Marcel NelenHans Scheffer, Dorien Lugtenberg, Frans Pm Cremers, Lies Hoefsloot, Helger G. Yntema

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99 Citations (Scopus)

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
Original languageEnglish
Pages (from-to)591-599
Number of pages9
JournalEuropean journal of human genetics
Volume25
Issue number5
Early online date2017
DOIs
Publication statusPublished - 1 May 2017

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