An Unusual Presentation of Novel Missense Variant in PAX6 Gene: NM_000280.4:c.341A>G, p.(Asn114Ser)
-
Published:2023-12-22
Issue:1
Volume:46
Page:96-105
-
ISSN:1467-3045
-
Container-title:Current Issues in Molecular Biology
-
language:en
-
Short-container-title:CIMB
Author:
Vasilyeva Tatyana A.1, Sukhanova Natella V.1ORCID, Khalanskaya Olga V.1, Marakhonov Andrey V.1ORCID, Prokhorov Nikolai S.2ORCID, Kadyshev Vitaly V.1ORCID, Skryabin Nikolay A.3ORCID, Kutsev Sergey I.1, Zinchenko Rena A.1ORCID
Affiliation:
1. Research Centre for Medical Genetics, 115522 Moscow, Russia 2. Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN 47405, USA 3. Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia
Abstract
This study investigates a unique and complex eye phenotype characterized by minimal iris defects, foveal hypoplasia, optic nerve coloboma, and severe posterior segment damage. Through genetic analysis and bioinformatic tools, a specific nonsynonymous substitution, p.(Asn114Ser), within the PAX6 gene’s paired domain is identified. Although this substitution is not in direct contact with DNA, its predicted stabilizing effect on the protein structure challenges the traditional understanding of PAX6 mutations, suggesting a gain-of-function mechanism. Contrary to classical loss-of-function effects, this gain-of-function hypothesis aligns with research demonstrating PAX6’s dosage sensitivity. Gain-of-function mutations, though less common, can lead to diverse phenotypes distinct from aniridia. Our findings emphasize PAX6’s multifaceted influence on ocular phenotypes and the importance of genetic variations. We contribute a new perspective on PAX6 mutations by suggesting a potential gain-of-function mechanism and showcasing the complexities of ocular development. This study sheds light on the intricate interplay of the genetic alterations and regulatory mechanisms underlying complex eye phenotypes. Further research, validation, and collaboration are crucial to unravel the nuanced interactions shaping ocular health and development.
Subject
Microbiology (medical),Molecular Biology,General Medicine,Microbiology
Reference30 articles.
1. Aniridia;Hingorani;Eur. J. Hum. Genet.,2012 2. Tzoulaki, I., White, I.M., and Hanson, I.M. (2005). Pax6 mutations: Genotype-phenotype correlations. BMC Genet., 6. 3. Mutations of the pax6 gene detected in patients with a variety of optic-nerve malformations;Azuma;Am. J. Hum. Genet.,2003 4. Matsushita, I., Izumi, H., Ueno, S., Hayashi, T., Fujinami, K., Tsunoda, K., Iwata, T., Kiuchi, Y., and Kondo, H. (2023). Functional characteristics of diverse pax6 mutations associated with isolated foveal hypoplasia. Genes, 14. 5. Functional properties of natural human pax6 and pax6(5a) mutants;Chauhan;Investig. Ophthalmol. Vis. Sci.,2004
|
|