{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:07:32Z","timestamp":1791400052411,"version":"4.3.3"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,12,27]],"date-time":"2014-12-27T00:00:00Z","timestamp":1419638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"King Faisal Specialist Hospital & Research Centre, Riyadh","award":["2020023"],"award-info":[{"award-number":["2020023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The pathologic basis of systemic juvenile idiopathic arthritis (JIA) is a subject of some controversy, with evidence for both autoimmune and autoinflammatory etiologies. Several monogenic autoinflammatory disorders have been described, but thus far, systemic JIA has only been attributed to a mutation of <jats:italic>MEFV<\/jats:italic> in rare cases and has been weakly associated with the HLA class II locus. This study was undertaken to identify the cause of an autosomal\u2010recessive form of systemic JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied 13 patients with systemic JIA from 5 consanguineous families, all from the southern region of Saudi Arabia. We used linkage analysis, homozygosity mapping, and whole\u2010exome sequencing to identify the disease\u2010associated gene and mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Linkage analysis localized systemic JIA to a region on chromosome 13 with a maximum logarithm of odds score of 11.33, representing the strongest linkage identified to date for this disorder. Homozygosity mapping reduced the critical interval to a 1.02\u2010Mb region defined proximally by rs9533338 and distally by rs9595049. Whole\u2010exome sequencing identified a homoallelic missense mutation in <jats:italic>LACC1<\/jats:italic>, which encodes the enzyme laccase (multicopper oxidoreductase) domain\u2013containing 1. The mutation was confirmed by Sanger sequencing and segregated with disease in all 5 families based on an autosomal\u2010recessive pattern of inheritance and complete penetrance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings provide strong genetic evidence of an association of a mutation in <jats:italic>LACC1<\/jats:italic> with systemic JIA in the families studied. Association of <jats:italic>LACC1<\/jats:italic> with Crohn's disease and leprosy has been reported and justifies investigation of its role in autoinflammatory disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38877","type":"journal-article","created":{"date-parts":[[2014,9,12]],"date-time":"2014-09-12T14:46:58Z","timestamp":1410533218000},"page":"288-295","source":"Crossref","is-referenced-by-count":138,"title":["Association of a Mutation in <i>LACC1<\/i> With a Monogenic Form of Systemic Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"67","author":[{"given":"Salma M.","family":"Wakil","sequence":"first","affiliation":[{"name":"King Faisal Specialist Hospital and Research Centre, and King Abdulaziz City for Science and Technology Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota M.","family":"Monies","sequence":"additional","affiliation":[{"name":"King Faisal Specialist Hospital and Research Centre, and King Abdulaziz City for Science and Technology Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abouelhoda","sequence":"additional","affiliation":[{"name":"King Faisal Specialist Hospital and Research Centre, and King Abdulaziz City for Science and Technology Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Al\u2010Tassan","sequence":"additional","affiliation":[{"name":"King Faisal Specialist Hospital and Research Centre, and King Abdulaziz City for Science and Technology Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haya","family":"Al\u2010Dusery","sequence":"additional","affiliation":[{"name":"King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa A.","family":"Naim","sequence":"additional","affiliation":[{"name":"King Faisal Specialist Hospital and Research Centre, and King Abdulaziz City for Science and Technology Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banan","family":"Al\u2010Younes","sequence":"additional","affiliation":[{"name":"King Faisal Specialist Hospital and Research Centre, and King Abdulaziz City for Science and Technology Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jameela","family":"Shinwari","sequence":"additional","affiliation":[{"name":"King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futwan A.","family":"Al\u2010Mohanna","sequence":"additional","affiliation":[{"name":"King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian F.","family":"Meyer","sequence":"additional","affiliation":[{"name":"King Faisal Specialist Hospital and Research Centre, and King Abdulaziz City for Science 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