{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:31:58Z","timestamp":1790951518892,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:00:00Z","timestamp":1683763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013405","name":"RVO","doi-asserted-by":"publisher","award":["(VFN, 64165)"],"award-info":[{"award-number":["(VFN, 64165)"]}],"id":[{"id":"10.13039\/100013405","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NV18-03-00227"],"award-info":[{"award-number":["NV18-03-00227"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NU21-05-00522"],"award-info":[{"award-number":["NU21-05-00522"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Somatic mutations in <jats:italic>UBA1<\/jats:italic> have recently been causally linked to a severe adult\u2010onset inflammatory condition referred to as VEXAS (vacuoles, E1 enzyme, X\u2010linked, autoinflammatory, somatic) syndrome. Ubiquitin\u2010activating enzyme E1 (UBA\u20101) is of fundamental importance to the modulation of ubiquitin homeostasis and to the majority of downstream ubiquitylation\u2010dependent cellular processes. Direct sequencing analysis of exon 3 containing the prevalent variants p.Met41Leu, p.Met41Val, and\/or p.Met41Thr is usually used to confirm the disease\u2010associated mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied the clinical, biochemical, and molecular genetic characteristics of a 59\u2010year\u2010old man with a 2\u2010year history of arthritis, fever, night sweats, nonspecific skin rash, lymphadenopathy, and myelodysplastic syndrome with multilineage dysplasia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mutational analysis revealed a previously undescribed sequence variant c.1430G&gt;C in exon 14 (p.Gly477Ala) in the gene <jats:italic>UBA1<\/jats:italic>. In vitro enzymatic analyses showed that p.Gly477Ala led to both decreased E1 ubiquitin thioester formation and E2 enzyme charging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We report a case of a patient of European ancestry with clinical manifestations of VEXAS syndrome associated with a newly identified dysfunctional UBA\u20101 enzyme variant. Due to the patient's insufficient response to various immunosuppressive treatments, allogeneic hematopoietic stem cell transplantation was performed, which resulted in significant improvement of clinical and laboratory manifestations of the disease.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42471-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42471","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T03:21:03Z","timestamp":1675999263000},"page":"1285-1290","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Novel Somatic <scp><i>UBA1<\/i><\/scp> Variant in a Patient With <scp>VEXAS<\/scp> Syndrome"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2465-1476","authenticated-orcid":false,"given":"Blanka","family":"Stiburkova","sequence":"first","affiliation":[{"name":"Institute of Rheumatology, Department of Rheumatology, and Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine Charles University and General University Hospital  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Pavelcova","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9158-881X","authenticated-orcid":false,"given":"Monika","family":"Belickova","sequence":"additional","affiliation":[{"name":"Institute of Hematology and Blood Transfusion  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5345-217X","authenticated-orcid":false,"given":"Samuel J.","family":"Magaziner","sequence":"additional","affiliation":[{"name":"Center for Human Genetics and Genomics, New York University School of Medicine  New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason C.","family":"Collins","sequence":"additional","affiliation":[{"name":"National Institute for Dental and Craniofacial Research, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Werner","sequence":"additional","affiliation":[{"name":"National Institute for Dental and Craniofacial Research, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Beck","sequence":"additional","affiliation":[{"name":"Center for Human Genetics and Genomics, and Division of Rheumatology, Department of Medicine New York University School of Medicine  New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Balajkova","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0021-3247","authenticated-orcid":false,"given":"Cyril","family":"Salek","sequence":"additional","affiliation":[{"name":"Institute of Hematology and Blood Transfusion, and Institute of Clinical and Experimental Haematology, First Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Vostry","sequence":"additional","affiliation":[{"name":"Institute of Hematology and Blood Transfusion  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Mann","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Vencovsky","sequence":"additional","affiliation":[{"name":"Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41992"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2026834"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2021.06.006"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.20805"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2021.10.002"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004976"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2021.10.006"},{"key":"e_1_2_7_9_1","first-page":"3591","article-title":"VEXAS syndrome","volume":"137","author":"Grayson 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