{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:59:16Z","timestamp":1790251156831,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,1,28]],"date-time":"2010-01-28T00:00:00Z","timestamp":1264636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Chronic infantile neurologic, cutaneous, articular syndrome (CINCA), also known as neonatal\u2010onset multisystem inflammatory disease (NOMID), is a severe, early\u2010onset autoinflammatory disease characterized by an urticaria\u2010like rash, arthritis\/arthropathy, variable neurologic involvement, and dysmorphic features, which usually respond to interleukin\u20101 blockade. CINCA\/NOMID has been associated with dominant Mendelian inherited\n                      <jats:italic>NLRP3<\/jats:italic>\n                      mutations. However, conventional sequencing analyses detect true disease\u2010causing mutations in only \u223c55\u201360% of patients, which suggests the presence of genetic heterogeneity. We undertook the current study to assess the presence of somatic, nongermline\n                      <jats:italic>NLRP3<\/jats:italic>\n                      mutations in a sporadic case of CINCA\/NOMID.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical data, laboratory results, and information on treatment outcomes were gathered through direct interviews. Exhaustive genetic studies, including Sanger method sequencing, subcloning, restriction fragment length polymorphism assay, and pyrosequencing, were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The patient's CINCA\/NOMID was diagnosed based on clinical features (early onset of the disease, urticaria\u2010like rash, knee arthropathy, and dysmorphic features). The patient has exhibited a successful response to anakinra within the last 28 months. Analysis of\n                      <jats:italic>NLRP3<\/jats:italic>\n                      identified a novel heterozygous variant (p.D303H) that was detected in \u223c30\u201338% of circulating leukocytes. The absence of this variant in healthy controls and in the patient's parents suggested a de novo true disease\u2010causing mutation. Additional analyses showed that this novel mutation was present in both leukocyte subpopulations and epithelial cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings identify the novel p.D303H\n                      <jats:italic>NLRP3<\/jats:italic>\n                      variant in a Spanish patient with CINCA\/NOMID as a new disease\u2010causing mutation, which was detected as a somatic, nongermline mutation in hematopoietic and nonhematopoietic cell lineages. Our data provide new insight into the role of low\u2010level mosaicism in\n                      <jats:italic>NLRP3<\/jats:italic>\n                      as the pathophysiologic mechanism underlying cryopyrin\u2010associated periodic syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.27342","type":"journal-article","created":{"date-parts":[[2010,1,28]],"date-time":"2010-01-28T12:59:01Z","timestamp":1264683541000},"page":"1158-1166","source":"Crossref","is-referenced-by-count":81,"title":["A somatic\n                    <i>NLRP3<\/i>\n                    mutation as a cause of a sporadic case of chronic infantile neurologic, cutaneous, articular syndrome\/neonatal\u2010onset multisystem inflammatory disease: Novel evidence of the role of low\u2010level mosaicism as the pathophysiologic mechanism underlying mendelian inherited diseases"],"prefix":"10.1002","volume":"62","author":[{"given":"Juan I.","family":"Ar\u00f3stegui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma Dolores","family":"Lopez Salda\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariona","family":"Pascal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Clemente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Aymerich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Balaguer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Goel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Fournier del Castillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefa","family":"Rius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Plaza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"L\u00f3pez Robledillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manel","family":"Juan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Iba\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Yag\u00fce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,3,30]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141627"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22491"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng756"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/341357"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10688"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200009)43:9<2034::AID-ANR14>3.0.CO;2-J"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000068883"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(81)80961-4"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.3109\/03009748709102523"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-07-2531"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20633"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21404"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-094201"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2006.06.003"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00599-3"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00046-9"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200306193482523"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20033"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17401-1"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh652"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055137"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel269"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22022"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-200305000-00006"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/25292"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5742(03)00010-3"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0796-290"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81894-2"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/11956"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040036"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199801153380305"}],"container-title":["Arthritis 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