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The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye

The transcription factor PAX6 is essential in ocular development in vertebrates, being considered the master regulator of the eye. During eye development, it is essential for the correct patterning and formation of the multi-layered optic cup and it is involved in the developing lens and corneal epi...

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Autores principales: Lima Cunha, Dulce, Arno, Gavin, Corton, Marta, Moosajee, Mariya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947179/
https://www.ncbi.nlm.nih.gov/pubmed/31861090
http://dx.doi.org/10.3390/genes10121050
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author Lima Cunha, Dulce
Arno, Gavin
Corton, Marta
Moosajee, Mariya
author_facet Lima Cunha, Dulce
Arno, Gavin
Corton, Marta
Moosajee, Mariya
author_sort Lima Cunha, Dulce
collection PubMed
description The transcription factor PAX6 is essential in ocular development in vertebrates, being considered the master regulator of the eye. During eye development, it is essential for the correct patterning and formation of the multi-layered optic cup and it is involved in the developing lens and corneal epithelium. In adulthood, it is mostly expressed in cornea, iris, and lens. PAX6 is a dosage-sensitive gene and it is highly regulated by several elements located upstream, downstream, and within the gene. There are more than 500 different mutations described to affect PAX6 and its regulatory regions, the majority of which lead to PAX6 haploinsufficiency, causing several ocular and systemic abnormalities. Aniridia is an autosomal dominant disorder that is marked by the complete or partial absence of the iris, foveal hypoplasia, and nystagmus, and is caused by heterozygous PAX6 mutations. Other ocular abnormalities have also been associated with PAX6 changes, and genotype-phenotype correlations are emerging. This review will cover recent advancements in PAX6 regulation, particularly the role of several enhancers that are known to regulate PAX6 during eye development and disease. We will also present an updated overview of the mutation spectrum, where an increasing number of mutations in the non-coding regions have been reported. Novel genotype-phenotype correlations will also be discussed.
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spelling pubmed-69471792020-01-13 The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye Lima Cunha, Dulce Arno, Gavin Corton, Marta Moosajee, Mariya Genes (Basel) Review The transcription factor PAX6 is essential in ocular development in vertebrates, being considered the master regulator of the eye. During eye development, it is essential for the correct patterning and formation of the multi-layered optic cup and it is involved in the developing lens and corneal epithelium. In adulthood, it is mostly expressed in cornea, iris, and lens. PAX6 is a dosage-sensitive gene and it is highly regulated by several elements located upstream, downstream, and within the gene. There are more than 500 different mutations described to affect PAX6 and its regulatory regions, the majority of which lead to PAX6 haploinsufficiency, causing several ocular and systemic abnormalities. Aniridia is an autosomal dominant disorder that is marked by the complete or partial absence of the iris, foveal hypoplasia, and nystagmus, and is caused by heterozygous PAX6 mutations. Other ocular abnormalities have also been associated with PAX6 changes, and genotype-phenotype correlations are emerging. This review will cover recent advancements in PAX6 regulation, particularly the role of several enhancers that are known to regulate PAX6 during eye development and disease. We will also present an updated overview of the mutation spectrum, where an increasing number of mutations in the non-coding regions have been reported. Novel genotype-phenotype correlations will also be discussed. MDPI 2019-12-17 /pmc/articles/PMC6947179/ /pubmed/31861090 http://dx.doi.org/10.3390/genes10121050 Text en © 2019 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 Review
Lima Cunha, Dulce
Arno, Gavin
Corton, Marta
Moosajee, Mariya
The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye
title The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye
title_full The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye
title_fullStr The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye
title_full_unstemmed The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye
title_short The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye
title_sort spectrum of pax6 mutations and genotype-phenotype correlations in the eye
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947179/
https://www.ncbi.nlm.nih.gov/pubmed/31861090
http://dx.doi.org/10.3390/genes10121050
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