{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T23:05:51Z","timestamp":1785539151604,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2021-1061"],"award-info":[{"award-number":["075-15-2021-1061"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["RF 193021X0029"],"award-info":[{"award-number":["RF 193021X0029"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Federal scientific\u2013technical program for genetic technologies development for 2019\u20132027","award":["075-15-2021-1061"],"award-info":[{"award-number":["075-15-2021-1061"]}]},{"name":"Federal scientific\u2013technical program for genetic technologies development for 2019\u20132027","award":["RF 193021X0029"],"award-info":[{"award-number":["RF 193021X0029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>This study investigates a unique and complex eye phenotype characterized by minimal iris defects, foveal hypoplasia, optic nerve coloboma, and severe posterior segment damage. Through genetic analysis and bioinformatic tools, a specific nonsynonymous substitution, p.(Asn114Ser), within the PAX6 gene\u2019s paired domain is identified. Although this substitution is not in direct contact with DNA, its predicted stabilizing effect on the protein structure challenges the traditional understanding of PAX6 mutations, suggesting a gain-of-function mechanism. Contrary to classical loss-of-function effects, this gain-of-function hypothesis aligns with research demonstrating PAX6\u2019s dosage sensitivity. Gain-of-function mutations, though less common, can lead to diverse phenotypes distinct from aniridia. Our findings emphasize PAX6\u2019s multifaceted influence on ocular phenotypes and the importance of genetic variations. We contribute a new perspective on PAX6 mutations by suggesting a potential gain-of-function mechanism and showcasing the complexities of ocular development. This study sheds light on the intricate interplay of the genetic alterations and regulatory mechanisms underlying complex eye phenotypes. Further research, validation, and collaboration are crucial to unravel the nuanced interactions shaping ocular health and development.<\/jats:p>","DOI":"10.3390\/cimb46010008","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T01:19:42Z","timestamp":1703207982000},"page":"96-105","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Unusual Presentation of Novel Missense Variant in PAX6 Gene: NM_000280.4:c.341A&gt;G, p.(Asn114Ser)"],"prefix":"10.3390","volume":"46","author":[{"given":"Tatyana A.","family":"Vasilyeva","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga V.","family":"Khalanskaya","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9621-0245","authenticated-orcid":false,"given":"Nikolai S.","family":"Prokhorov","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7765-3307","authenticated-orcid":false,"given":"Vitaly V.","family":"Kadyshev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2491-3141","authenticated-orcid":false,"given":"Nikolay A.","family":"Skryabin","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey I.","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/ejhg.2012.100","article-title":"Aniridia","volume":"20","author":"Hingorani","year":"2012","journal-title":"Eur. 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