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Application of medical technology for the diagnosis of congenital aniridia at the research centre for medical genetics

Abstract

Congenital aniridia is a Mendelian autosomal dominant panocular disorder with complete penetrance and variable expressivity. The incidence of aniridia is 1 in 40,000-100,000 births. Aniridia is characterized by congenital absence of the iris with foveal hypoplasia and other eye abnormalities. Aniridia occurs as non-syndromic which, however, often affects all eye structures (75% of cases) and syndromic (20%, including WAGR syndrome). The most cases of aniridia, both isolated and syndromic, is caused by heterozygous mutations in the PAX6 gene or chromosome 11p13 rearrangements. Large deletions of the same region affecting PAX6 and WT1 genes loci lead to the WAGR syndrome. 110 patients with a preliminary diagnosis of congenital aniridia from 84 unrelated families and 7 patients from 7 unrelated families diagnosed with WAGR syndrome were included into the study. The applied complex confirmatory and differential DNA diagnosis of aniridia and WAGR syndrome consists of two main sequential steps: MLPA analysis (with confirmation of the detected deletions using the loss of heterozygosity analysis and/or FISH) and Sanger sequencing. The efficiency of MLPA analysis as an initial diagnostic method is 33% (30/91). The effectiveness of sequencing as the only method for diagnosis of aniridia is 63.7% (58/91). As a result of the application of complex medical technology at the Research Centre for Medical Genetics, the diagnosis was confirmed in 107 patients (81 probands) with aniridia and 7 patients with WAGR syndrome. Frequent PAX6 mutations and 11p13 deletions were identified. The effectiveness of two-staged technology for congenital aniridia diagnosis is 96.7% (88/91).

About the Authors

A. V. Marakhonov
Research Center for Medical Genetics; Moscow Institute of Physics and Technology (State University)
Russian Federation


T. A. Vasilyeva
Research Center for Medical Genetics
Russian Federation


A. A. Voskresenskaya
Cheboksary branch of S. Fyodorov Eye Microsurgery Federal State Institution
Russian Federation


V. V. Kadyshev
Research Center for Medical Genetics
Russian Federation


N. A. Pozdeyeva
Cheboksary branch of S. Fyodorov Eye Microsurgery Federal State Institution
Russian Federation


N. V. Shilova
Research Center for Medical Genetics
Russian Federation


S. I. Braslavskaya
Research Center for Medical Genetics
Russian Federation


O. V. Khlebnikova
Research Center for Medical Genetics
Russian Federation


R. A. Zinchenko
Research Center for Medical Genetics; Pirogov Russian National Research Medical University
Russian Federation


S. I. Kutsev
Research Center for Medical Genetics; Pirogov Russian National Research Medical University
Russian Federation


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Review

For citations:


Marakhonov A.V., Vasilyeva T.A., Voskresenskaya A.A., Kadyshev V.V., Pozdeyeva N.A., Shilova N.V., Braslavskaya S.I., Khlebnikova O.V., Zinchenko R.A., Kutsev S.I. Application of medical technology for the diagnosis of congenital aniridia at the research centre for medical genetics. Medical Genetics. 2017;16(11):23-26. (In Russ.)

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ISSN 2073-7998 (Print)