Association of a Mutation in LACC1 With a Monogenic Form of Systemic Juvenile Idiopathic Arthritis. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Wakil, Salma M.; Monies, Dorota M.; Abouelhoda, Mohamed; Al‐Tassan, Nada; Al‐Dusery, Haya; Naim, Ewa A.; Al‐Younes, Banan; Shinwari, Jameela; Al‐Mohanna, Futwan A.; Meyer, Brian F.; Al‐Mayouf, Sulaiman
• Is Part Of: Arthritis & rheumatology. Volume 67:Issue 1(2015)
• Page Start: 288
• Page End: 295
• Publication Date: 2015-01
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.38877
• Languages: English
• ISSNs: 2326-5191

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art38877-sec-0001" sec-type="section"> <title>Objective</title> <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 <italic>MEFV</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‐recessive form of systemic JIA.</p> </sec> <sec id="art38877-sec-0002" sec-type="section"> <title>Methods</title> <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‐exome sequencing to identify the disease‐associated gene and mutation.</p> </sec> <sec id="art38877-sec-0003" sec-type="section"> <title>Results</title> <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‐Mb region defined proximally by rs9533338 and distally by rs9595049. Whole‐exome sequencing identified a homoallelic missense mutation in <italic>LACC1</italic>, which encodes the enzyme laccase (multicopper oxidoreductase) domain–containing 1. The mutation was confirmed by Sanger sequencing and segregated with disease in all 5 families based on an autosomal‐recessive pattern of inheritance and complete penetrance.</p> </sec> <sec id="art38877-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Our findings provide strong genetic evidence of an association of a mutation in <italic>LACC1</italic> with systemic JIA in the families studied. Association of <italic>LACC1</italic> with Crohn's disease and leprosy has been reported and justifies investigation of its role in autoinflammatory disorders.</p> </sec> </abstract>