{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T05:45:38Z","timestamp":1750657538043,"version":"3.37.3"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T00:00:00Z","timestamp":1572220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T00:00:00Z","timestamp":1572220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012280","name":"The Rare Disease Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012280","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Arthritis Society \u2013 Ross Petty Chair in Pediatric Rheumatology start-up fund"},{"name":"Michael Smith Foundation for Health Research and Cassie & Friends Society Scholar Award"},{"name":"BC Children\u2019s Hospital Research Institute IGAP award"},{"name":"Andrew Nord Graduate Student Award in Rheumatology"},{"name":"Cassie & Friends International Postdoctoral Fellowship"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n              <jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Despite recent advances in the diagnosis and understanding of many autoinflammatory diseases, there are still a great number of patients with phenotypes that do not fit any clinically- and\/or genetically-defined disorders.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>We describe a fourteen-year-old boy who presented at two and a half years of age with recurrent febrile episodes. Over the course of the disease, the episodes increased in frequency and severity, with new signs and symptoms continuing to appear. Most importantly, these included skin changes, splenomegaly and transaminitis. Only partial control of the disease was achieved with anti-IL-1 therapy. Extensive investigation showed generalized inflammation without immune deficiency, with increased levels of serum amyloid A and several pro-inflammatory cytokines including interferon-\u03b3, as well as an increased type I interferon score. Exome sequence analysis identified P369S and R408Q variants in the MEFV innate immunity regulator, pyrin (<jats:italic>MEFV)<\/jats:italic> gene and T260\u2009M and T320\u2009M variants in the NLR family pyrin domain containing 12 (<jats:italic>NLRP12<\/jats:italic>) gene.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Patients with unclassified and\/or unexplained autoinflammatory syndromes present diagnostic and therapeutic challenges and collectively form a substantial part of every cohort of patients with autoinflammatory diseases. Therefore, it is important to acquire their full genomic profile through whole exome and\/or genome sequencing and present their cases to a broader audience, to facilitate characterization of similar patients. A critical mass of well-characterized cases will lead to improved diagnosis and informed treatment.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12969-019-0374-x","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T15:05:26Z","timestamp":1572275126000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Complexity in unclassified auto-inflammatory disease: a case report illustrating the potential for disease arising from the allelic burden of multiple variants"],"prefix":"10.1186","volume":"17","author":[{"given":"Lori B.","family":"Tucker","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7939-115X","authenticated-orcid":false,"given":"Lovro","family":"Lamot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iwona","family":"Niemietz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian K.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Cabral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Houghton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross E.","family":"Petty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly A.","family":"Morishita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian I.","family":"Rice","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart E.","family":"Turvey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William T.","family":"Gibson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly L.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,10,28]]},"reference":[{"key":"374_CR1","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1146\/annurev.immunol.25.022106.141627","volume":"27","author":"SL Masters","year":"2009","unstructured":"Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*). Annu Rev Immunol. 2009;27:621\u201368.","journal-title":"Annu Rev Immunol"},{"key":"374_CR2","first-page":"501305","volume":"2013","author":"A Marcuzzi","year":"2013","unstructured":"Marcuzzi A, Piscianz E, Kleiner G, Tommasini A, Severini GM, Monasta L, et al. Clinical genetic testing of periodic fever syndromes. Biomed Res Int. 2013;2013:501305.","journal-title":"Biomed Res Int"},{"issue":"11","key":"374_CR3","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1093\/rheumatology\/keu170","volume":"53","author":"RA Russo","year":"2014","unstructured":"Russo RA, Brogan PA. Monogenic autoinflammatory diseases. Rheumatology (Oxford). 2014;53(11):1927\u201339.","journal-title":"Rheumatology (Oxford)"},{"issue":"4","key":"374_CR4","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.berh.2017.12.001","volume":"31","author":"HJ Lachmann","year":"2017","unstructured":"Lachmann HJ. Periodic fever syndromes. Best Pract Res Clin Rheumatol. 2017;31(4):596\u2013609.","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"374_CR5","doi-asserted-by":"crossref","unstructured":"Rice GI, Forte GM, Szynkiewicz M, Chase DS, Aeby A, Abdel-Hamid MS, et al. Assessment of interferon-related Rice GI, Forte GM, Szynkiewicz M, Chase DS, Aeby A, Abdel-Hamid MS, et al. Assessment of interferon-related biomarkers in Aicardi-Goutieres syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol. 2013;12(12):1159-69.","DOI":"10.1016\/S1474-4422(13)70258-8"},{"issue":"3","key":"374_CR6","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1136\/archdischild-2016-310772","volume":"102","author":"ES Sen","year":"2017","unstructured":"Sen ES, Steward CG, Ramanan AV. Diagnosing haemophagocytic syndrome. 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Written informed consent was obtained from the patient, siblings and\/or parents. Samples obtained from otherwise healthy children were enrolled to the BCCH BioBank (H13\u201303111).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors obtained verbal consent for publication from patient and parents.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"70"}}