Rabionet, RaquelRemesal, AgustínMensa Vilaró, AnnaMurías, SaraAlcobendas, RosaGonzález-Roca, EvaRuíz Ortiz, EstíbalizAntón, JordiIglesias, EstibalizModesto, ConsueloComas, David, 1969-Puig, AnnaDrechsel, OliverOssowski, StephanYagüe, Jordi L.Merino, RosaEstivill, Xavier, 1955-Aróstegui Gorospe, Juan Ignacio2019-03-262019-03-262019Rabionet R, Remesal A, Mensa-Vilaró A, Murías S, Alcobendas R, González-Roca E et al. Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis. Sci Rep. 2019;9(1):4579. DOI: 10.1038/s41598-019-40874-22045-2322http://hdl.handle.net/10230/36963Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease with both autoimmune and autoinflammatory components. Recently, familial cases of systemic-onset JIA have been attributed to mutations in LACC1/FAMIN. We describe three affected siblings from a Moroccan consanguineous family with an early-onset chronic, symmetric and erosive arthritis previously diagnosed as rheumatoid factor (RF)-negative polyarticular JIA. Autozygosity mapping identified four homozygous regions shared by all patients, located in chromosomes 3, 6 (n:2) and 13, containing over 330 genes. Subsequent whole exome sequencing identified two potential candidate variants within these regions (in FARS2 and LACC1/FAMIN). Genotyping of a cohort of healthy Moroccan individuals (n: 352) and bioinformatics analyses finally supported the frameshift c.128_129delGT mutation in the LACC1/FAMIN gene, leading to a truncated protein (p.Cys43Tyrfs*6), as the most probable causative gene defect. Additional targeted sequencing studies performed in patients with systemic-onset JIA (n:23) and RF-negative polyarticular JIA (n: 44) revealed no pathogenic LACC1/FAMIN mutations. Our findings support the homozygous genotype in the LACC1/FAMIN gene as the defect underlying the family here described with a recessively inherited severe inflammatory joint disease. Our evidences provide further support to the involvement of LACC1/FAMIN deficiency in different types of JIA in addition to the initially described systemic-onset JIA.application/pdfeng© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-019-40874-2Disease geneticsJuvenile idiopathic arthritisinfo:eu-repo/semantics/openAccess