Clinical and genetic characteristics of a total or partial congenital aniridia
DOI: 10.32364/2311-7729-2023-23-1-2-8
N.V. Sukhanova1, V.V. Kadyshev1, T.A. Vasilieva1, A.V. Marakhonov1, L.A. Katargina 2, S.I. Kutsev1, R.A. Zinchenko1,3
1Research Center for Medical Genetics, Moscow, Russian Federation
2Helmholtz National Medical Research Center for Eye Diseases, Moscow, Russian Federation
3N.A. Semashko National Research Institute of Public Health, Moscow, Russian Federation
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 fr om 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 wh ere 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.
About the authors:
Natella V. Sukhanova — ophthalmologist of the Scientific and Clinical Center for Genetics of Eye Diseases, researcher of the Laboratory of Genetic Epidemiology, Research Center for Medical Genetics; 1, Moskvorechye str., Moscow, 115522, Russian Federation; ORCID iD 0000-0003-4371-775X.
Vitaly V. Kadyshev — C. Sc. (Med.), leading researcher of the Laboratory of Genetic Epidemiology; geneticist, ophthalmologist of the Scientific and Clinical Center for Genetics of Eye Diseases, Research Center for Medical Genetics; Head of the Department of Ophthalmic Genetics of the Institute of the Higher and Additional Professional Education, Research Center for Medical Genetics; 1, Moskvorechye str., Moscow, 115522, Russian Federation; ORCID iD 0000-0001-7765-3307.
Tatyana A. Vasilieva — C. Sc. (Biol.), senior researcher of the Laboratory of Genetic Epidemiology, Research Center for Medical Genetics; 1, Moskvorechye str., Moscow, 115522, Russian Federation; ORCID iD 0000-0002-6744-0567.
Andrey V. Marakhonov — C. Sc. (Biol.), leading researcher of the Laboratory of Genetic Epidemiology, Research Center for Medical Genetics; 1, Moskvorechye str., Moscow, 115522, Russian Federation; ORCID iD 0000-0002-0972-5118.
Lyudmila A. Katargina — Dr. Sc. (Med.), Professor, Deputy Director for Research, Helmholtz National Medical Research Center for Eye Diseases; 14/19, Sadovaya-Chernogryazskaya str., Moscow, 105062, Russian Federation; ORCID iD 0000-0002-4857-0374.
Sergey I. Kutsev — Dr. Sc. (Med.), Academician of the Russian Academy of Sciences, Director, Research Center for Medical Genetics; Chief External Expert of the Ministry of Health of the Russian Federation; 1, Moskvorechye str., Moscow, 115522, Russian Federation; ORCID iD 0000-0002-3133-8018.
Rena A. Zinchenko — Dr. Sc. (Med.), Corresponding Member of the Russian Academy of Sciences, Deputy Director for Research and Clinical Activities, Head of the Laboratory of Genetic Epidemiology, Research Center for Medical Genetics; Head of the Department of Public Healthcare Organization, Public Health and Medical Genetic Monitoring of the Institute of the Higher and Additional Professional Education, Research Center for Medical Genetics; 1, Moskvorechye str., Moscow, 115522, Russian Federation; chief researcher of the Department of Public Health Studies, N.A. Semashko National Research Institute of Public Health; 12 build. 1, Vorontsovo Pole str., Moscow, 105064, Russian Federation; ORCID iD 0000-0003-3586-3458.
Contact information: Natella V. Sukhanova, e-mail: natelasukhanova@gmail.com.
Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.
There is no conflict of interests.
Received 28.09.2022.
Revised 20.10.2022.
Accepted 15.11.2022.
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