{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T03:25:54Z","timestamp":1793244354617,"version":"4.5.0"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Signal transducer and activator of transcription 3 (<jats:italic>STAT3<\/jats:italic>) is a member of the STAT protein family implicated in the development of infantile-onset multisystem autoimmune disease. <jats:italic>STAT3<\/jats:italic>-related autoimmune disease is characterized by multiorgan autoimmunity, lymphoproliferative disease, and recurrent infections. The presentation is variable, with some patients also developing neonatal diabetes mellitus and interstitial lung disease. Gain-of-function variants in the Src homology 2 domain, leading to autophosphorylation and activation of <jats:italic>STAT3<\/jats:italic>, have been previously reported in patients with disease. Here, we report a patient with a novel missense variant, p.Glu616Ala, in <jats:italic>STAT3<\/jats:italic> presenting with infantile-onset multisystem autoimmune disease.<\/jats:p>","DOI":"10.3389\/fmed.2023.1251088","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T04:28:40Z","timestamp":1699849720000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel STAT3 variant causing infantile-onset autoimmune disease"],"prefix":"10.3389","volume":"10","author":[{"given":"Miao","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Kurtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1126\/science.8272872","article-title":"Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130","volume":"263","author":"L\u00fctticken","year":"1994","journal-title":"Science"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1080\/15548627.2015.1017192","article-title":"The role of STAT3 in 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neonatal diabetes through reduced insulin synthesis","volume":"66","author":"Velayos","year":"2017","journal-title":"Diabetes"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1358\/dof.2011.036.11.1710754","article-title":"GAD65 autoantibodies and its role as biomarker of type 1 diabetes and latent autoimmune diabetes in adults (LADA)","volume":"36","author":"Towns","year":"2011","journal-title":"Drugs Future"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"359674","DOI":"10.1155\/2013\/359674","article-title":"STAT3 regulates proliferation and survival of CD8+ T cells: enhances effector responses to HSV-1 infection, and inhibits IL-10+ regulatory CD8+ T cells in autoimmune uveitis","volume":"2013","author":"Yu","year":"2013","journal-title":"Mediat Inflamm"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e20210759","DOI":"10.1084\/jem.20210759","article-title":"A human mutation in STAT3 promotes type 1 diabetes through a defect in CD8+ T cell tolerance","volume":"218","author":"Warshauer","year":"2021","journal-title":"J Exp Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1016\/j.jaci.2018.07.020","article-title":"Jakinibs for the treatment of immune dysregulation in patients with gain-of-function signal transducer and activator of transcription 1 (STAT1) or STAT3 mutations","volume":"142","author":"Forbes","year":"2018","journal-title":"J Allergy Clin Immunol"}],"container-title":["Frontiers in 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