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Ocular Phenotype Associated with DYRK1A Variants

Dual-specificity tyrosine phosphorylation-regulated kinase 1A or DYRK1A, contributes to central nervous system development in a dose-sensitive manner. Triallelic DYRK1A is implicated in the neuropathology of Down syndrome, whereas haploinsufficiency causes the rare DYRK1A-related intellectual disabi...

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Autores principales: Méjécase, Cécile, Way, Christopher M., Owen, Nicholas, Moosajee, Mariya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915179/
https://www.ncbi.nlm.nih.gov/pubmed/33562844
http://dx.doi.org/10.3390/genes12020234
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author Méjécase, Cécile
Way, Christopher M.
Owen, Nicholas
Moosajee, Mariya
author_facet Méjécase, Cécile
Way, Christopher M.
Owen, Nicholas
Moosajee, Mariya
author_sort Méjécase, Cécile
collection PubMed
description Dual-specificity tyrosine phosphorylation-regulated kinase 1A or DYRK1A, contributes to central nervous system development in a dose-sensitive manner. Triallelic DYRK1A is implicated in the neuropathology of Down syndrome, whereas haploinsufficiency causes the rare DYRK1A-related intellectual disability syndrome (also known as mental retardation 7). It is characterised by intellectual disability, autism spectrum disorder and microcephaly with a typical facial gestalt. Preclinical studies elucidate a role for DYRK1A in eye development and case studies have reported associated ocular pathology. In this study families of the DYRK1A Syndrome International Association were asked to self-report any co-existing ocular abnormalities. Twenty-six patients responded but only 14 had molecular confirmation of a DYRK1A pathogenic variant. A further nineteen patients from the UK Genomics England 100,000 Genomes Project were identified and combined with 112 patients reported in the literature for further analysis. Ninety out of 145 patients (62.1%) with heterozygous DYRK1A variants revealed ocular features, these ranged from optic nerve hypoplasia (13%, 12/90), refractive error (35.6%, 32/90) and strabismus (21.1%, 19/90). Patients with DYRK1A variants should be referred to ophthalmology as part of their management care pathway to prevent amblyopia in children and reduce visual comorbidity, which may further impact on learning, behaviour, and quality of life.
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spelling pubmed-79151792021-03-01 Ocular Phenotype Associated with DYRK1A Variants Méjécase, Cécile Way, Christopher M. Owen, Nicholas Moosajee, Mariya Genes (Basel) Article Dual-specificity tyrosine phosphorylation-regulated kinase 1A or DYRK1A, contributes to central nervous system development in a dose-sensitive manner. Triallelic DYRK1A is implicated in the neuropathology of Down syndrome, whereas haploinsufficiency causes the rare DYRK1A-related intellectual disability syndrome (also known as mental retardation 7). It is characterised by intellectual disability, autism spectrum disorder and microcephaly with a typical facial gestalt. Preclinical studies elucidate a role for DYRK1A in eye development and case studies have reported associated ocular pathology. In this study families of the DYRK1A Syndrome International Association were asked to self-report any co-existing ocular abnormalities. Twenty-six patients responded but only 14 had molecular confirmation of a DYRK1A pathogenic variant. A further nineteen patients from the UK Genomics England 100,000 Genomes Project were identified and combined with 112 patients reported in the literature for further analysis. Ninety out of 145 patients (62.1%) with heterozygous DYRK1A variants revealed ocular features, these ranged from optic nerve hypoplasia (13%, 12/90), refractive error (35.6%, 32/90) and strabismus (21.1%, 19/90). Patients with DYRK1A variants should be referred to ophthalmology as part of their management care pathway to prevent amblyopia in children and reduce visual comorbidity, which may further impact on learning, behaviour, and quality of life. MDPI 2021-02-05 /pmc/articles/PMC7915179/ /pubmed/33562844 http://dx.doi.org/10.3390/genes12020234 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Méjécase, Cécile
Way, Christopher M.
Owen, Nicholas
Moosajee, Mariya
Ocular Phenotype Associated with DYRK1A Variants
title Ocular Phenotype Associated with DYRK1A Variants
title_full Ocular Phenotype Associated with DYRK1A Variants
title_fullStr Ocular Phenotype Associated with DYRK1A Variants
title_full_unstemmed Ocular Phenotype Associated with DYRK1A Variants
title_short Ocular Phenotype Associated with DYRK1A Variants
title_sort ocular phenotype associated with dyrk1a variants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915179/
https://www.ncbi.nlm.nih.gov/pubmed/33562844
http://dx.doi.org/10.3390/genes12020234
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