{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:36:34Z","timestamp":1790181394587,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000066","name":"Canadian Child Health Clinician Scientist Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001245","name":"Jeffrey Modell Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013891","name":"Immunodeficiency Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013891","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>STAT1\u00a0gain\u2010of\u2010function (GOF) is an immune dysregulatory disorder with poorly studied genotype\u2010phenotype correlation, impeding prognostication and early intervention. Given previous mechanistic studies, as well as anecdotal clinical reports, we sought to systematically determine whether DNA\u2010binding domain (DBD) mutations in STAT1 result in a different phenotype than mutations in other gene domains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Negative prognostic features previously identified by the International STAT1 GOF Study Group (invasive infections, intracranial aneurysms, and malignancy), as well as other clinical features and mortality, were compared within a cohort of 30 patients with STAT1 GOF diagnosed at our center, consisting of 9 patients with DBD mutations and 21 patients with non\u2010DBD mutations. We subsequently re\u2010analyzed mortality data from a large, previously\u2010published 274\u2010patient cohort by the International STAT1 GOF Study Group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>While no differences were noted with respect to malignancy or symptomatic aneurysms, invasive \/opportunistic infections were substantially more common among DBD patients, as were sinopulmonary infections, bronchiectasis, enteropathy, endocrinopathies, lymphoproliferative manifestations, and recurrent fevers\/HLH. DBD patients also had a lower probability of survival and younger age of mortality compared with non\u2010DBD patients. Our re\u2010evaluation of the published data from the International STAT1 GOF Study Group revealed a similar finding of earlier mortality among patients harboring DBD mutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We report that STAT1 GOF patients with DBD mutations may be regarded as a unique subgroup, impacted more by early\u2010onset profound combined immunodeficiency and with earlier mortality. These findings may impact clinical decision making with respect to early intervention, and in particular hematopoietic stem cell transplant considerations, in such patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.13694","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T09:34:37Z","timestamp":1636104877000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["DNA\u2010Binding domain mutations confer severe outcome at an early age among STAT1 gain\u2010of\u2010function patients"],"prefix":"10.1111","volume":"33","author":[{"given":"Ori","family":"Scott","sequence":"first","affiliation":[{"name":"Division of Immunology and Allergy Department of Paediatrics Hospital for Sick Children and University of Toronto Toronto Ontario 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B.","family":"Mandola","sequence":"additional","affiliation":[{"name":"Pediatrics Department A Soroka University Medical Center Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rae","family":"Brager","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Immunology, and Allergy Department of Paediatrics McMaster Children's Hospital McMaster University Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hostoffer","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care University Hospitals Cleveland Medical Center Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Nahum","sequence":"additional","affiliation":[{"name":"Pediatrics Department A Soroka University Medical Center Beer\u2010Sheva Israel"},{"name":"The Primary Immunodeficiency Research Laboratory Faculty of Health Sciences 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