{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T12:21:56Z","timestamp":1792412516383,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2002,12,12]],"date-time":"2002-12-12T00:00:00Z","timestamp":1039651200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2002,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Neonatal\u2010onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome) is characterized by fever, chronic meningitis, uveitis, sensorineural hearing loss, urticarial skin rash, and a characteristic deforming arthropathy. We investigated whether patients with this disorder have mutations in\n                      <jats:italic>CIAS1<\/jats:italic>\n                      , the gene which causes Muckle\u2010Wells syndrome and familial cold autoinflammatory syndrome, two dominantly inherited disorders with some similarities to NOMID\/CINCA syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Genomic DNA from 13 patients with classic manifestations of NOMID\/CINCA syndrome and their available parents was screened for\n                      <jats:italic>CIAS1<\/jats:italic>\n                      mutations by automated DNA sequencing. Cytokine messenger RNA (mRNA) levels were assessed by real\u2010time polymerase chain reaction on peripheral blood leukocyte mRNA, and serum cytokine levels were assayed by enzyme\u2010linked immunosorbent assay. Protein expression was assessed by Western blotting of lysates from plastic\u2010adherent peripheral blood mononuclear cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 6 of the 13 patients, we found 6 heterozygous missense substitutions in\n                      <jats:italic>CIAS1.<\/jats:italic>\n                      Five of the 6 mutations are novel. None of these sequence changes was observed in a panel of &gt;900 chromosomes from healthy controls. Two distinct nucleotide changes in a single codon in unrelated patients resulted in the same amino acid change. In 4 mutation\u2010positive children whose parental DNA was available, no mutation was found in the parental DNA, supporting the conclusion that the mutations arose de novo. Consistent with the recently discovered role of\n                      <jats:italic>CIAS1<\/jats:italic>\n                      in the regulation of interleukin\u20101 (IL\u20101), we found evidence of increased IL\u20101\u03b2, as well as tumor necrosis factor, IL\u20103, IL\u20105, and IL\u20106, but not transforming growth factor \u03b2, in a mutation\u2010positive patient compared with normal controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our data increase the total number of known germline mutations in\n                      <jats:italic>CIAS1<\/jats:italic>\n                      to 20, causing a spectrum of diseases ranging from familial cold autoinflammatory syndrome to Muckle\u2010Wells syndrome to NOMID\/CINCA syndrome. Mutations in\n                      <jats:italic>CIAS1<\/jats:italic>\n                      were only found in \u223c50% of the cases identified clinically as NOMID\/CINCA syndrome, which raises the possibility of genetic heterogeneity. IL\u20101 regulation by\n                      <jats:italic>CIAS1<\/jats:italic>\n                      suggests that IL\u20101 receptor blockade may constitute a rational approach to the treatment of NOMID\/CINCA syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.10688","type":"journal-article","created":{"date-parts":[[2002,12,16]],"date-time":"2002-12-16T08:50:56Z","timestamp":1040028656000},"page":"3340-3348","source":"Crossref","is-referenced-by-count":623,"title":["De novo\n                    <i>CIAS1<\/i>\n                    mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal\u2010onset multisystem inflammatory disease (NOMID): A new member of the expanding family of pyrin\u2010associated autoinflammatory diseases"],"prefix":"10.1002","volume":"46","author":[{"given":"Ivona","family":"Aksentijevich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslawa","family":"Nowak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustapha","family":"Mallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Jin","family":"Chae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy T.","family":"Watford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrun 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