{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T11:54:01Z","timestamp":1772711641272,"version":"3.50.1"},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T00:00:00Z","timestamp":1567555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Signal Transducer and Activator of Transcription 1 (STAT1) is a DNA\u2010binding signal transducer that regulates transcription of specific genes in response to IFN\u03b3 and IFN\u03b1\/\u03b2 stimulation. Loss\u2010of\u2010function mutations impairing STAT1 activity are known to confer susceptibility to intracellular bacterial and viral diseases. Conversely, the few known activating mutations of STAT1 allow predisposition to chronic mucocutaneous candidiasis disease, and occur in patients with combined immunodeficiency and defective Th1 and Th17 responses. Here, we report on a\n                    <jats:italic>de novo<\/jats:italic>\n                    gain\u2010of\u2010function (GoF)\n                    <jats:italic>STAT1<\/jats:italic>\n                    mutation (c.1398C&gt;G, p.Ser466Arg) identified by exome sequencing in an individual with brain calcification, arthritis, recurrent pericarditis, leukopenia, thrombocytopenia and low C3 levels, a phenotype resembling an interferonopathy. The Ser466Arg change affects a highly conserved residue located in the DNA binding domain of the protein and the amino acid substitution was documented to have an activating role both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Altogether, clinical features and functional studies are compatible with hyperactivation of the Interferon pathways, highlighting a role of\n                    <jats:italic>STAT1<\/jats:italic>\n                    GoF mutation in clinical phenotypes fitting interferonopathies.\n                  <\/jats:p>","DOI":"10.1111\/cge.13632","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T01:54:27Z","timestamp":1566784467000},"page":"585-589","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The activating p.Ser466Arg change in STAT1 causes a peculiar phenotype with features of interferonopathies"],"prefix":"10.1111","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0415-3285","authenticated-orcid":false,"given":"Emilia","family":"Stellacci","sequence":"first","affiliation":[{"name":"Dipartimento di Oncologia e Medicina Molecolare Istituto Superiore di Sanit\u00e0  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gian M.","family":"Moneta","sequence":"additional","affiliation":[{"name":"Dipartimento Pediatrie Specialistiche, U. O. Reumatologia Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Bruselles","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia e Medicina Molecolare Istituto Superiore di Sanit\u00e0  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7307-388X","authenticated-orcid":false,"given":"Sabina","family":"Barresi","sequence":"additional","affiliation":[{"name":"Area di Ricerca Genetica e Malattie Rare Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Pizzi","sequence":"additional","affiliation":[{"name":"Area di Ricerca Genetica e Malattie Rare Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuliano","family":"Torre","sequence":"additional","affiliation":[{"name":"Dipartimento Pediatrie Specialistiche, U. O. Reumatologia Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"De Benedetti","sequence":"additional","affiliation":[{"name":"Dipartimento Pediatrie Specialistiche, U. O. Reumatologia Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Area di Ricerca Genetica e Malattie Rare Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Insalaco","sequence":"additional","affiliation":[{"name":"Dipartimento Pediatrie Specialistiche, U. O. Reumatologia Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,9,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R700016200"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1100102"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-015-0214-9"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-679902"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110958"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.10.051"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.03.049"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.8.984"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-016-0094-4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.11.022"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.08.040"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-016-0312-3"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key276"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13632","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.13632","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13632","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T10:08:31Z","timestamp":1694167711000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,4]]},"references-count":13,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1111\/cge.13632"],"URL":"https:\/\/doi.org\/10.1111\/cge.13632","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.13632\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13632\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13632\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13632\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13632\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13632\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,4]]},"assertion":[{"value":"2019-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}