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Open AccessReview

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

1
Institute of Ophthalmology, UCL, London EC1V 9EL, UK
2
Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK
3
Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK
4
Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital—Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain
5
Centre for Biomedical Network Research on Rare Diseases (CIBERER), 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
Genes 2019, 10(12), 1050; https://doi.org/10.3390/genes10121050
Received: 15 November 2019 / Revised: 9 December 2019 / Accepted: 12 December 2019 / Published: 17 December 2019
(This article belongs to the Special Issue Recent Advances in Inherited Eye Disease)
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. View Full-Text
Keywords: aniridia; enhancers; genotype-phenotype correlations; haploinsufficiency; PAX6; paired domain; microphthalmia; non-coding variants; premature termination codon; regulatory regions aniridia; enhancers; genotype-phenotype correlations; haploinsufficiency; PAX6; paired domain; microphthalmia; non-coding variants; premature termination codon; regulatory regions
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MDPI and ACS Style

Lima Cunha, D.; Arno, G.; Corton, M.; Moosajee, M. The Spectrum of PAX6 Mutations and Genotype-Phenotype Correlations in the Eye. Genes 2019, 10, 1050.

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