{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:37:23Z","timestamp":1760150243900,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T00:00:00Z","timestamp":1699056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Foundation","award":["22-25-00824"],"award-info":[{"award-number":["22-25-00824"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>This study investigates the distribution of PAX6-associated congenital aniridia (AN) and WAGR syndrome across Russian Federation (RF) districts while characterizing PAX6 gene variants. We contribute novel PAX6 pathogenic variants and 11p13 chromosome region rearrangements to international databases based on a cohort of 379 AN patients (295 families, 295 probands) in Russia. We detail 100 newly characterized families (129 patients) recruited from clinical practice and specialized screening studies. Our methodology involves multiplex ligase-dependent probe amplification (MLPA) analysis of the 11p13 chromosome, PAX6 gene Sanger sequencing, and karyotype analysis. We report novel findings on PAX6 gene variations, including 67 intragenic PAX6 variants and 33 chromosome deletions in the 100 newly characterized families. Our expanded sample of 295 AN families with 379 patients reveals a consistent global PAX6 variant spectrum, including CNVs (copy number variants) of the 11p13 chromosome (31%), complex rearrangements (1.4%), nonsense (25%), frameshift (18%), and splicing variants (15%). No genetic cause of AN is defined in 10 patients. The distribution of patients across the Russian Federation varies, likely due to sample completeness. This study offers the first AN epidemiological data for the RF, providing a comprehensive PAX6 variants spectrum. Based on earlier assessment of AN prevalence in the RF (1:98,943) we have revealed unexamined patients ranging from 55% to 87%, that emphases the need for increased awareness and comprehensive diagnostics in AN patient care in Russia.<\/jats:p>","DOI":"10.3390\/genes14112041","type":"journal-article","created":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T14:51:01Z","timestamp":1699109461000},"page":"2041","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Epidemiology of PAX6 Gene Pathogenic Variants and Expected Prevalence of PAX6-Associated Congenital Aniridia across the Russian Federation: A Nationwide Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Tatyana A.","family":"Vasilyeva","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-5118","authenticated-orcid":false,"given":"Andrey V.","family":"Marakhonov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4213-4923","authenticated-orcid":false,"given":"Anna A.","family":"Voskresenskaya","sequence":"additional","affiliation":[{"name":"Fyodorov Eye Microsurgery Federal State Institution Cheboksary Branch, 428028 Cheboksary, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vitaly V.","family":"Kadyshev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4371-775X","authenticated-orcid":false,"given":"Natella V.","family":"Sukhanova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5458-0408","authenticated-orcid":false,"given":"Marina E.","family":"Minzhenkova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-1084","authenticated-orcid":false,"given":"Nadezhda V.","family":"Shilova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alla A.","family":"Latyshova","sequence":"additional","affiliation":[{"name":"Russian Research Institute of Health, 127254 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeny K.","family":"Ginter","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey I.","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3586-3458","authenticated-orcid":false,"given":"Rena A.","family":"Zinchenko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1167\/iovs.08-2827","article-title":"Detailed ophthalmologic evaluation of 43 individuals with pax6 mutations","volume":"50","author":"Hingorani","year":"2009","journal-title":"Investig. 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