Article Text

Download PDFPDF
Short report
Analysis of genotype–phenotype correlations in PAX6-associated aniridia
  1. Tatyana A. Vasilyeva1,
  2. Andrey V. Marakhonov1,
  3. Anna A. Voskresenskaya2,
  4. Vitaly V. Kadyshev1,
  5. Barbara Käsmann-Kellner3,
  6. Natella V. Sukhanova4,
  7. Lyudmila A. Katargina4,
  8. Sergey I. Kutsev1,
  9. Rena A. Zinchenko1
  1. 1 Laboratory of Genetic Epidemiology, Research Centre for Medical Genetics, Moscow, Russian Federation
  2. 2 Cheboksary Branch of S. Fyodorov Eye Microsurgery Federal State Institution, Cheboksary, Russian Federation
  3. 3 Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg, Saarland, Germany
  4. 4 Moscow Helmholtz Research Institute of Eye Diseases, Moscow, Russian Federation
  1. Correspondence to Dr Andrey V. Marakhonov, Research Centre for Medical Genetics, Moscow, Russian Federation; marakhonov{at}



Aniridia is a severe autosomal dominant panocular disorder associated with pathogenic sequence variants of the PAX6 gene or 11p13 chromosomal aberrations encompassing the coding and/or regulatory regions of the PAX6 gene in a heterozygous state. Patients with aniridia display several ocular anomalies including foveal hypoplasia, cataract, keratopathy, and glaucoma, which can vary in severity and combination.


A cohort of 155 patients from 125 unrelated families with identified point PAX6 pathogenic variants (118 patients) or large chromosomal 11p13 deletions (37 patients) was analyzed. Genetic causes were divided into 6 types. The occurrence of 6 aniridic eye anomalies was analyzed. Fisher’s exact test was applied for 2×2 contingency tables assigning numbers of patients with/without each sign and each type of the PAX6 variants or 11p13 deletions with Benjamini–Hochberg correction. The age of patients with different types of mutation did not differ.


Patients with 3′-cis-regulatory region deletions had a milder aniridia phenotype without keratopathy, nystagmus, or foveal hypoplasia. The phenotypes of the patients with other rearrangements involving 11p13 do not significantly differ from those associated with point pathogenic variants in the PAX6 gene. Missense mutations and genetic variants disrupting splicing are associated with a severe aniridia phenotype and resemble loss-of-function mutations. It is particularly important that in all examined patients, PAX6 mutations were found to be associated with multiple eye malformations. The age of patients with keratopathy, cataract, and glaucoma was significantly higher than the age of patients without these signs.


We got clear statistically significant genotype-phenotype correlations in congenital aniridia and evident that aniridia severity indeed had worsened with age.

  • congenital aniridia
  • PAX6pathogenic variants
  • chromosome region 11p13 deletions
  • 3′-cis-regulatory region deletions, genotype–phenotype correlations

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • TAV and AVM are joint first authors.

  • TAV and AVM contributed equally.

  • Contributors TAV, AVM, BK-K, LAK, SIK and RAZ contributed to the conception and design of the study. TAV, AVM, NVS, AAV, VVK, BK-K and RAZ contributed to the acquisition and analysis of data. TAV and AVM drafted the text.

  • Funding This work was supported in part by the Russian Science Foundation grant 17-15-01051 and the state assignment of Ministry of Science and Higher Education of the Russian Federation. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Institutional Review Board of the Research Centre for Medical Genetics, Moscow, Russia (approval no. 2017-4/1 dated 4 May 2017).

  • Provenance and peer review Not commissioned; externally peer reviewed.