PAX6 Gene Characteristic and Causative Role of PAX6 Mutations in Inherited Eye Pathologies
- Authors: Vasilyeva T.A.1, Voskresenskaya A.A.2, Pozdeyeva N.A.2, Marakhonov A.V.1,3, Zinchenko R.A.1,4
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Affiliations:
- Research Center for Medical Genetics
- Cheboksary Branch, Fyodorov Eye Microsurgery Federal State Institution
- Moscow Institute of Physics and Technology (State University)
- Pirogov Russian National Research Medical University
- Issue: Vol 54, No 9 (2018)
- Pages: 995-1002
- Section: Reviews and Theoretical Articles
- URL: https://journals.rcsi.science/1022-7954/article/view/189129
- DOI: https://doi.org/10.1134/S1022795418090156
- ID: 189129
Cite item
Abstract
The PAX6 gene encodes one of the key embryonic transcription factors and serves as a master regulator of eye and central nervous system morphogenesis in all species of bilaterian animals. The PAX6 protein contains two DNA binding domains: paired and homeobox. To ensure specific regulation of target genes, the domains are able to bind different DNA motifs either independently or in cooperation or even antagonizing in different cell contexts. PAX6 has a complex temporal and tissue-specific expression pattern. Abnormal levels of its expression, either excessive or insufficient, as well as a misbalanced ratio of expressed transcript variants, lead to the disturbance of embryogenesis. Compound heterozygous mutations in the PAX6 gene are lethal. Most heterozygous mutations lead to the loss of function of mutated PAX6 allele (haploinsufficiency). PAX6 function deficiency results in several phenotypes. The most frequent one is congenital aniridia (>90%), which is characterized by damage to various eye structures often accompanied by morphological and functional disorders of other organs and systems. The reasons for the varying expressiveness of mutant alleles of the PAX6 gene and the development of various phenotypes are still poorly understood. This review deals with the analysis of the current state of knowledge about the normal structure and functions of the PAX6 gene and its encoded protein, as well as the phenotypes associated with various mutations of this gene in humans.
About the authors
T. A. Vasilyeva
Research Center for Medical Genetics
Author for correspondence.
Email: vasilyeva_debrie@mail.ru
Russian Federation, Moscow, 115478
A. A. Voskresenskaya
Cheboksary Branch, Fyodorov Eye Microsurgery Federal State Institution
Email: vasilyeva_debrie@mail.ru
Russian Federation, Cheboksary, 428028
N. A. Pozdeyeva
Cheboksary Branch, Fyodorov Eye Microsurgery Federal State Institution
Email: vasilyeva_debrie@mail.ru
Russian Federation, Cheboksary, 428028
A. V. Marakhonov
Research Center for Medical Genetics; Moscow Institute of Physics and Technology (State University)
Email: vasilyeva_debrie@mail.ru
Russian Federation, Moscow, 115478; Dolgoprudny, Moscow oblast, 141701
R. A. Zinchenko
Research Center for Medical Genetics; Pirogov Russian National Research Medical University
Email: vasilyeva_debrie@mail.ru
Russian Federation, Moscow, 115478; Moscow, 117997