Epidemiology of PAX6 Gene Pathogenic Variants and Expected Prevalence of PAX6-Associated Congenital Aniridia across the Russian Federation: A Nationwide Study

Vasilyeva, Tatyana A.; Marakhonov, Andrey V.; Voskresenskaya, Anna A.; Kadyshev, Vitaly V.; Sukhanova, Natella V.; Minzhenkova, Marina E.; Shilova, Nadezhda V.; Latyshova, Alla A.; Ginter, Evgeny K.; Kutsev, Sergey I.; Zinchenko, Rena A.

doi:10.3390/genes14112041

Cited by 1 publication

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References 23 publications

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“…Genomic DNA was isolated from peripheral blood using a Promega ® kit according to the manufacturer's recommendations. Copy number variations in the 11p13 locus were analyzed by multiplex ligase-dependent probe amplification (MLPA) analysis, and intragenic PAX6 sequence variants were screened by Sanger sequencing, as mentioned earlier [10].…”

Section: Case Presentation Materials and Methodsmentioning

confidence: 99%

An Unusual Presentation of Novel Missense Variant in PAX6 Gene: NM_000280.4:c.341A>G, p.(Asn114Ser)

Vasilyeva,

Sukhanova,

Khalanskaya

et al. 2023

CIMB

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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.

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Section: Case Presentation Materials and Methodsmentioning

confidence: 99%