Clinical and genetic characteristics of a total or partial congenital aniridia

Aim: to assess clinical and genetic correlations between the specific clinical manifestations of congenital aniridia (CA) and the spectrum of mutations in the PAX6 gene (including chromosomal deletions involving the entire PAX6 gene or its regions). Patients and Methods: the study included 83 patients from 76 unrelated families with clinical patterns of congenital aniridia. The mean age of patients was 11.5±10.3 years. All patients underwent a comprehensive eye exam, molecular and genetic testing, as well as specialist consultation. To find a genetic cause of CA, the analysis of minor mutations in the PAX6 gene was performed by Sanger sequencing in order to determine the nucleotide sequence of 13 exons and adjacent intronic regions. Also, the number of gene copies of a chromosomal region 11p13 was evaluated by using multiplex reaction of Ligation-dependent Probe Amplification (MLPA) assay. In those cases where a chromosomal deletion involving the WT1 gene was detected, a target fluorescent in situ hybridization (FISH) with a locus-specific DNA- probe for the WT1 gene was carried out to prove the MLPA results. The functional in vitro analysis of the impact of intronic nucleotide sequence variants was performed in the laboratory of functional genomics of the Research Center for Medical Genetics (RCMG) using the original technique. Results: the most common features associated with CA included foveal hypoplasia, nystagmus, disorders of the eye lens, and limbal stem cells deficiency (LSCD). These findings were reported in more than 60% of cases. Partial CA was significantly more prevalent in patients with splice- site mutations (p=0.004996) as compared to other mutation types. Optic nerve hypoplasia (p=0.04779), internal strabismus (p=0.010882), aniridia-associated keratopathy co-occurring with LSCD (p=0.013236) were diagnosed more frequently in patients with nonsense mutations. Secondary glaucoma was a more common finding in patients with the deletion of 3'-cis-regulatory region (p=0.020381). Conclusion: the analysis of genotypic and phenotypic correlations has revealed statistical regularities which may underpin the relationship between the clinical pattern of CA and the types of mutations. Keywords: congenital aniridia, foveal hypoplasia, PAX6, mutations, features of the clinical picture, geno-phenotypic correlations. For citation: Sukhanova N.V., Kadyshev V.V., Vasilieva T.A. et al. Clinical and genetic characteristics of a total or partial congenital aniridia. Russian Journal of Clinical Ophthalmology. 2023;23(1):2–8 (in Russ.). DOI: 10.32364/2311-7729-2023-23-1-2-8.