{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:32:37Z","timestamp":1762900357084,"version":"3.41.2"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Almost 5% of the world's population develops an autoimmune disease (AID), it is considered the fourth leading cause of disability for women, who represent 78% of cases. The sex ratio when it comes to the most prevalent AID varies from 9:1 in systemic lupus erythematosus (SLE) to 13:1 in endemic Tunisian pemphigus foliaceus (PF).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To test the potential involvement of skewed x\u2010inactivation in the pathogenesis of Tunisian PF, we analyzed the methylation status of a highly polymorphic CAG repeat in the androgen receptor gene and evaluated the x chromosome inactivation (XCI) patterns in peripheral blood\u2010leukocyte\u2010derived DNA samples of female patients with PF (<jats:italic>n<\/jats:italic>\u00a0=\u00a098) compared to healthy control (HC) subjects (<jats:italic>n<\/jats:italic>\u00a0=\u00a0150), as well as female patients with SLE (<jats:italic>n<\/jats:italic>\u00a0=\u00a098) were enrolled as a reference group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>XCI status was informative for 50 of the 98 PF patients (51%) and 70 of the 150 HC women (47%). Extremely skewed XCI patterns were more frequent in PF and SLEwomen than HC, but the difference was statistically significant only in women with SLE. No statistical difference was observed in XCI patterns between PF and SLE patients. PF phenotype\u2010XCI correlation analysis revealed that (i) skewed XCI patterns may be involved in the disease's subtype and (ii) it was more pronounced in the endemic group than the sporadic one. Furthermore, preferential XCI showed an increase in heterozygote genotypes of PF's susceptibility polymorphisms in immunity\u2010related X genes (<jats:italic>FOXP3<\/jats:italic>, <jats:italic>AR,<\/jats:italic> and <jats:italic>TLR7<\/jats:italic>) in PF patients compared to HC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that skewed XCI could lead to hemizygosity of X\u2010linked alleles that might unmask X\u2010linked deleterious alleles.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2080","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T09:43:45Z","timestamp":1667987025000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of X chromosome inactivation in endemic Tunisian pemphigus foliaceus"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0208-145X","authenticated-orcid":false,"given":"Olfa","family":"Abida","sequence":"first","affiliation":[{"name":"\u201cAutoimmunity, Cancer and Immunogenetics\u201d Research Laboratory (LR18SP12), Immunology Department, Habib Bourguiba Hospital University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6154-5854","authenticated-orcid":false,"given":"Nesrine","family":"Elloumi","sequence":"additional","affiliation":[{"name":"\u201cAutoimmunity, Cancer and Immunogenetics\u201d Research Laboratory (LR18SP12), Immunology Department, Habib Bourguiba Hospital University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emna","family":"Bahloul","sequence":"additional","affiliation":[{"name":"Dermatology Department, HediChaker Hospital University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hend","family":"Hachicha","sequence":"additional","affiliation":[{"name":"\u201cAutoimmunity, Cancer and Immunogenetics\u201d Research Laboratory (LR18SP12), Immunology Department, Habib Bourguiba Hospital University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khadija","family":"Sellami","sequence":"additional","affiliation":[{"name":"Dermatology Department, HediChaker Hospital University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5379-0622","authenticated-orcid":false,"given":"Raouia","family":"Fakhfakh","sequence":"additional","affiliation":[{"name":"\u201cAutoimmunity, Cancer and Immunogenetics\u201d Research Laboratory (LR18SP12), Immunology Department, Habib Bourguiba Hospital University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sameh","family":"Marzouk","sequence":"additional","affiliation":[{"name":"Internal Medicine, HediChaker Hospital University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikhlas","family":"Ben Ayed","sequence":"additional","affiliation":[{"name":"Genetic Department, HediChaker Hospital University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Mahfoudh","sequence":"additional","affiliation":[{"name":"Immunology Department, HediChaker Hospital University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamida","family":"Turki","sequence":"additional","affiliation":[{"name":"Dermatology Department, HediChaker Hospital University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatem","family":"Masmoudi","sequence":"additional","affiliation":[{"name":"\u201cAutoimmunity, Cancer and Immunogenetics\u201d Research Laboratory (LR18SP12), Immunology Department, Habib Bourguiba Hospital University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6541761"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468\u20103083.2009.03265.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102133.2009.09386.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102133.2009.09207.x"},{"issue":"6","key":"e_1_2_10_6_1","first-page":"1229","article-title":"Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen\u2010receptor gene correlates with X chromosome inactivation","volume":"51","author":"Allen R. C.","year":"1992","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523\u20101747.ep12612836"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/155.3.249"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2017.02.005"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2011.11.012"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399\u20100004.2000.580504.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.04.007"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2759"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13957"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523\u20101747.ep13070394"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.1.575"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6153"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24962"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3231"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.9.6352"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.MR0318\u2010132R"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1993.01680220081019"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2011.11.001"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21026"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016\u2010007\u20108051\u20100"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199801293380611"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102133.1988.tb02590.x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916934.2017.1329830"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2008.09.002"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0167\u20105699(98)01298\u20105"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.24966\/CDT\u20108771\/100017"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100380170099"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016\u2010007\u20108044\u2010z"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23475"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2080","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.2080","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2080","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T06:12:33Z","timestamp":1692684753000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,9]]},"references-count":33,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/mgg3.2080"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2080","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2022,11,9]]},"assertion":[{"value":"2021-11-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2080"}}