Whole exome sequencing of known eye genes reveals genetic causes for high myopia.

Autor:	Haarman AEG; Department of Ophthalmology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.; Department of Epidemiology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands., Thiadens AAHJ; Department of Ophthalmology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands., van Tienhoven M; Department of Clinical Genetics, Erasmus MC, 3000 CA, Rotterdam, The Netherlands., Loudon SE; Department of Ophthalmology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands., de Klein JEMMA; Department of Clinical Genetics, Erasmus MC, 3000 CA, Rotterdam, The Netherlands., Brosens E; Department of Clinical Genetics, Erasmus MC, 3000 CA, Rotterdam, The Netherlands., Polling JR; Department of Ophthalmology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.; Department of Orthoptics, School of Applied Science Utrecht, 3584 CH, Utrecht, The Netherlands., van der Schoot V; Department of Clinical Genetics, Erasmus MC, 3000 CA, Rotterdam, The Netherlands., Bouman A; Department of Clinical Genetics, Erasmus MC, 3000 CA, Rotterdam, The Netherlands., Kievit AJA; Department of Clinical Genetics, Erasmus MC, 3000 CA, Rotterdam, The Netherlands., Hoefsloot LH; Department of Clinical Genetics, Erasmus MC, 3000 CA, Rotterdam, The Netherlands., Klaver CCW; Department of Ophthalmology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.; Department of Epidemiology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.; Department of Ophthalmology, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands.; Molecular research Center, Institute of Molecular and Clinical Ophthalmology, University of Basel, 4056, Switzerland., Verhoeven VJM; Department of Ophthalmology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.; Department of Clinical Genetics, Erasmus MC, 3000 CA, Rotterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Human molecular genetics [Hum Mol Genet] 2022 Sep 29; Vol. 31 (19), pp. 3290-3298.
DOI:	10.1093/hmg/ddac113
Abstrakt:	High myopia [refractive error ≤ -6 diopters (D)] is a heterogeneous condition, and without clear accompanying features, it can be difficult to pinpoint a genetic cause. This observational study aimed to evaluate the utility of whole exome sequencing (WES) using an eye disorder gene panel in European patients with high myopia. Patients with high myopia were recruited by ophthalmologists and clinical geneticists. Clinical features were categorized into isolated high myopia, high myopia with other ocular involvement or with systemic involvement. WES was performed and an eye disorder gene panel of ~500 genes was evaluated. Hundred and thirteen patients with high myopia [mean (SD) refractive error - 11.8D (5.2)] were included. Of these, 53% were children younger than 12 years of age (53%), 13.3% were aged 12-18 years and 34% were adults (aged > 18 years). Twenty-three out of 113 patients (20%) received a genetic diagnosis of which 11 patients displayed additional ocular or systemic involvement. Pathogenic variants were identified in retinal dystrophy genes (e.g. GUCY2D and CACNA1F), connective tissue disease genes (e.g. COL18A1 and COL2A1), non-syndromic high myopia genes (ARR3), ocular development genes (e.g. PAX6) and other genes (ASPH and CNNM4). In 20% of our high myopic study population, WES using an eye gene panel enabled us to diagnose the genetic cause for this disorder. Eye genes known to cause retinal dystrophy, developmental or syndromic disorders can cause high myopia without apparent clinical features of other pathology. (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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