{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T20:31:03Z","timestamp":1786739463570,"version":"build-2736575974"},"reference-count":17,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T00:00:00Z","timestamp":1604966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The classification and pathogenic basis of juvenile idiopathic arthritis (JIA) are a subject of some controversy. Essentially, JIA is an exclusion diagnosis that represents a phenotypically heterogeneous group of arthritis of unknown origin. Familial aggregation of JIA supports the concept of genetic influence in the pathogenesis of JIA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To present the spectrum of laccase domain-containing 1 (LACC1)-associated juvenile arthritis with clinical, biochemical, and molecular genetic data of a cohort of 43 patients, including 11 previously unpublished cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We studied 11 patients with different categories of juvenile idiopathic arthritis from 5 consanguineous families, all from Saudi Arabia, except 2 patients who were of Jordanian ethnicity. Whole-exome sequencing was used to identify the disease-causing variant of LACC1. We also reviewed the clinical spectrum and molecular genetic data of previously published cases of LACC1-associated juvenile arthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>This study describes 43 (29 females, 14 males) patients from consanguineous multiplex families. Most of the included patients were of Arab origin with 86% having early onset disease. The most frequent categories were systemic (19 patients) and rheumatoid factor-negative polyarticular (19 patients). Thirty-seven (86%) had progressive erosive arthritis and 10 (23.3%) had persistent limb lymphedema. None of the patients had features of macrophage activation syndrome. Genetic analysis confirmed LACC1 variant in all patients; 22 patients had common founder mutation (LACC1: c.850T &gt; C,p.C284R), while the others showed different LACC1 variants. All patients were treated aggressively with methotrexate and sequential biologic agents. Most of them showed a poor response to treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>This report expands the pathogenic variants of LACC1 and the clinical spectrum associated with this genetic subset of juvenile arthritis. The predominance of autosomal-recessive inheritance and strong genetic evidence allowed us to propose LACC1-associated juvenile arthritis as a distinct disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.ijpam.2020.11.005","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T05:31:29Z","timestamp":1605159089000},"page":"44-47","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["New or vanishing frontiers"],"prefix":"10.4103","volume":"8","author":[{"given":"Sulaiman M.","family":"Al-Mayouf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mada","family":"Yateem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haya","family":"Al-Dusery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Monies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Wakil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal","family":"AlShiakh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullatif","family":"AlEnazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boshra","family":"Aladaileh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raed","family":"Alzyoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-9-20240903","first-page":"390","article-title":"International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty","year":"2004","journal-title":"J Rheumatol"},{"key":"R2-9-20240903","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s40744-016-0040-4","article-title":"Juvenile idiopathic arthritis: diagnosis and treatment","volume":"3","author":"Giancane","year":"2016","journal-title":"Rheumatol Ther"},{"key":"R3-9-20240903","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/art.20815","article-title":"Nomenclature and classification in chronic childhood arthritis: time for a change?","volume":"52","author":"Duffy","year":"2005","journal-title":"Arthritis Rheum: Off J Am College Rheumatol"},{"key":"R4-9-20240903","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1097\/BOR.0000000000000094","article-title":"Genetics of JIA: new tools bring new approaches","volume":"26","author":"Moncrieffe","year":"2014","journal-title":"Curr Opin Rheumatol"},{"key":"R5-9-20240903","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1002\/art.40216","article-title":"Genome-wide association meta-analysis reveals novel juvenile idiopathic arthritis susceptibility loci","volume":"69","author":"McIntosh","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"R6-9-20240903","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/art.38877","article-title":"Association of a mutation in LACC1 with a monogenic form of systemic juvenile idiopathic arthritis","volume":"67","author":"Wakil","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"R7-9-20240903","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12969-016-0124-2","article-title":"Juvenile arthritis caused by a novel FAMIN (LACC1) mutation in two children with systemic and extended oligoarticular course","volume":"14","author":"Kallinich","year":"2016","journal-title":"Pediatr Rheumatol"},{"key":"R8-9-20240903","doi-asserted-by":"crossref","first-page":"726","DOI":"10.3899\/jrheum.170834","article-title":"LACC1 gene defects in familial form of juvenile arthritis","volume":"45","author":"Karacan","year":"2018","journal-title":"J Rheumatol"},{"key":"R9-9-20240903","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.1038\/s41598-019-40874-2","article-title":"Biallelic loss-of-function LACC1\/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis","volume":"9","author":"Rabionet","year":"2019","journal-title":"Sci Rep"},{"key":"R10-9-20240903","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1136\/annrheumdis-2019-216263","article-title":"LACC1 gene mutation in three sisters with polyarthritis without systemic features","volume":"79","author":"Singh","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"R11-9-20240903","first-page":"1","article-title":"edu. sa. 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