Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis

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• dc.contributor.author Rabionet, Raquel
• dc.contributor.author Remesal, Agustín
• dc.contributor.author Mensa Vilaró, Anna
• dc.contributor.author Murías, Sara
• dc.contributor.author Alcobendas, Rosa
• dc.contributor.author González-Roca, Eva
• dc.contributor.author Ruíz Ortiz, Estíbaliz
• dc.contributor.author Antón, Jordi
• dc.contributor.author Iglesias, Estibaliz
• dc.contributor.author Modesto, Consuelo
• dc.contributor.author Comas, David, 1969-
• dc.contributor.author Puig, Anna
• dc.contributor.author Drechsel, Oliver
• dc.contributor.author Ossowski, Stephan
• dc.contributor.author Yagüe, Jordi L.
• dc.contributor.author Merino, Rosa
• dc.contributor.author Estivill, Xavier, 1955-
• dc.contributor.author Aróstegui Gorospe, Juan Ignacio
• dc.date.accessioned 2019-03-26T09:37:48Z
• dc.date.available 2019-03-26T09:37:48Z
• dc.date.issued 2019
• dc.description.abstract Juvenile 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.
• dc.description.sponsorship This work has been partially funded by: CERCA Programme/Generalitat de Catalunya (JIA, XE, SO), the PERIS program of the Generalitat de Catalunya grant SLT002/16/00310 (RR), the Spanish Ministry of Economy and Competitiveness co-financed by European Regional Development Fund (ERDF) grant SAF2015-68472-C2-1-R (JIA), the Instituto de Salud Carlos III/Transnational Research Projects on Rare Diseases (JIA) grant AC15/00027, the Spanish Society of Pediatric Rheumatology (JIA), the Secretaria d’Universitats i Recerca del Departament d’Economia grant 2009-SGR-1502 (XE) and the European Union Seventh Framework Programme (FP7/2007-2013) grant agreement no. 262055 (XE).
• dc.format.mimetype application/pdf
• dc.identifier.citation Rabionet 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/s41598-019-40874-2
• dc.identifier.doi http://dx.doi.org/10.1038/s41598-019-40874-2
• dc.identifier.issn 2045-2322
• dc.identifier.uri http://hdl.handle.net/10230/36963
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Scientific Reports. 2019;9(1):4579
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-68472-C2-1-R
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/262055
• dc.rights © 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/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Disease genetics
• dc.subject.keyword Juvenile idiopathic arthritis
• dc.title Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion