{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T20:53:41Z","timestamp":1772052821847,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K07562"],"award-info":[{"award-number":["22K07562"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K07597"],"award-info":[{"award-number":["22K07597"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K07016"],"award-info":[{"award-number":["23K07016"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The main features of Axenfeld\u2013Rieger Syndrome (ARS) are ocular, auditory, neurological, and morphological brain abnormalities. Mutations in forkhead box protein C1 (FOXC1) are among the responsible genes causing ARS, but neuropsychiatric features have rarely been reported. The case of an ARS patient (a 77\u2010year\u2010old man) with delusions of jealousy and impairment of working memory, in addition to the main clinical features, glaucoma and leukoencephalopathy, is presented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The mutation in the patient's genome was found with whole exome sequencing and in silico analysis using PolyPhen\u20102 and SIFT. Furthermore, AlphaFold2 and PyMOL were used to predict the protein structure based on the mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel mutation at the forkhead domain of FOXC1 gene (c.408C&gt;A, p.Phe136Leu) was found and confirmed in the patient's family, and it was predicted to cause protein damage; the SIFT score was 0, meaning deleterious, and the PolyPhen2 result also indicated damaging (score: 0.997). The predicted protein structure based on the novel mutation was different from that of the native structure. In the literature review, 6 of 95 (6.3%) cases showed neuropsychiatric features. Of them, 5 of 6 (83.3%) mutations were located in the forkhead domain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A novel mutation was found in the FOXC1 gene (c.408C&gt;A, p.Phe136Leu), which possibly induces delusions of jealousy and impairment of working memory, as well as features of ARS, by changing the protein structure. Mutations in that domain of the FOXC1 gene may be important not only for ocular abnormalities but also for brain function.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70008","type":"journal-article","created":{"date-parts":[[2024,11,9]],"date-time":"2024-11-09T07:59:48Z","timestamp":1731139188000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Mutation of <scp>FOXC1<\/scp> (<scp>P136L<\/scp>) in an Axenfeld\u2013Rieger Syndrome Patient With a Systematized Delusion of Jealousy: A Case Report and Literature Review"],"prefix":"10.1002","volume":"12","author":[{"given":"Yuta","family":"Yoshino","sequence":"first","affiliation":[{"name":"Department of Neuropsychiatry, Molecules and Function Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4409-3096","authenticated-orcid":false,"given":"Jun\u2010ichi","family":"Iga","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Molecules and Function Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu\u2010ichi","family":"Ueno","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Molecules and Function Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2011-300801"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2293-3_19"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5309"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221810001"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI75109"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2016.08.020"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004058"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.169"},{"issue":"7","key":"e_1_2_10_13_1","article-title":"A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome With Congenital Glaucoma","volume":"11","author":"Micheal S.","year":"2016","journal-title":"Public Library of Science One"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e18225"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12816"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/pace.12537"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030787"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13148"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.59"},{"issue":"3","key":"e_1_2_10_20_1","first-page":"916","article-title":"Genetic Leukoencephalopathies in Adults","volume":"22","author":"Vanderver A.","year":"2016","journal-title":"Continuum"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T06:59:56Z","timestamp":1732690796000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":19,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/mgg3.70008"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70008","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70008"}}