EYS mutation update: In silico assessment of 271 reported and 26 novel variants in patients with retinitis pigmentosa |
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| Authors: | Muriël Messchaert Lonneke Haer‐Wigman Muhammad I. Khan Frans P. M. Cremers Rob W. J. Collin |
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| Affiliation: | 1. Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands;2. Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands |
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| Abstract: | Mutations in Eyes shut homolog (EYS) are one of the most common causes of autosomal recessive (ar) retinitis pigmentosa (RP), a progressive blinding disorder. The exact function of the EYS protein and the pathogenic mechanisms underlying EYS‐associated RP are still poorly understood, which hampers the interpretation of the causality of many EYS variants discovered to date. We collected all reported EYS variants present in 377 arRP index cases published before June 2017, and uploaded them in the Leiden Open Variation Database ( www.LOVD.nl/EYS ). We also describe 36 additional index cases, carrying 26 novel variants. Of the 297 unique EYS variants identified, almost half (n = 130) are predicted to result in premature truncation of the EYS protein. Classification of all variants using the American College of Medical Genetics and Genomics guidelines revealed that the predicted pathogenicity of these variants cover the complete spectrum ranging from likely benign to pathogenic, although especially missense variants largely fall in the category of uncertain significance. Besides the identification of likely benign alleles previously reported as being probably pathogenic, our comprehensive analysis underscores the need of functional assays to assess the causality of EYS variants, in order to improve molecular diagnostics and counseling of patients with EYS‐associated RP. |
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| Keywords: | EYS in silico assessment LOVD retinitis pigmentosa (RP) |
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