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

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...

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Autores: Rabionet Janssen, Raquel, Remesal, Agustín, Mensa Vilaró, Anna, Murías, Sara, Alcobendas, Rosa, González-Roca, Eva, Ruíz Ortiz, Estíbaliz, Antón, Jordi, Iglesias, Estibaliz, Modesto, Consuelo, Comas, David, 1969-, Puig, Anna, Drechsel, Oliver, Ossowski, Stephan, Yagüe, Jordi L., Merino, Rosa, Estivill, Xavier, 1955-, Aróstegui Gorospe, Juan Ignacio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/36963
Acceso en línea:http://hdl.handle.net/10230/36963
http://dx.doi.org/10.1038/s41598-019-40874-2
Access Level:acceso abierto
Palabra clave:Disease genetics
Juvenile idiopathic arthritis
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spelling Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritisRabionet Janssen, 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 IgnacioDisease geneticsJuvenile idiopathic arthritisJuvenile 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.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).Nature Research201920192019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/36963http://dx.doi.org/10.1038/s41598-019-40874-2reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésScientific Reports. 2019;9(1):4579info:eu-repo/grantAgreement/ES/1PE/SAF2015-68472-C2-1-Rinfo:eu-repo/grantAgreement/EC/FP7/262055© 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/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/369632026-06-12T07:21:37Z
dc.title.none.fl_str_mv Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
title Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
spellingShingle Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
Rabionet Janssen, Raquel
Disease genetics
Juvenile idiopathic arthritis
title_short Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
title_full Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
title_fullStr Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
title_full_unstemmed Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
title_sort Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
dc.creator.none.fl_str_mv Rabionet Janssen, Raquel
Remesal, Agustín
Mensa Vilaró, Anna
Murías, Sara
Alcobendas, Rosa
González-Roca, Eva
Ruíz Ortiz, Estíbaliz
Antón, Jordi
Iglesias, Estibaliz
Modesto, Consuelo
Comas, David, 1969-
Puig, Anna
Drechsel, Oliver
Ossowski, Stephan
Yagüe, Jordi L.
Merino, Rosa
Estivill, Xavier, 1955-
Aróstegui Gorospe, Juan Ignacio
author Rabionet Janssen, Raquel
author_facet Rabionet Janssen, Raquel
Remesal, Agustín
Mensa Vilaró, Anna
Murías, Sara
Alcobendas, Rosa
González-Roca, Eva
Ruíz Ortiz, Estíbaliz
Antón, Jordi
Iglesias, Estibaliz
Modesto, Consuelo
Comas, David, 1969-
Puig, Anna
Drechsel, Oliver
Ossowski, Stephan
Yagüe, Jordi L.
Merino, Rosa
Estivill, Xavier, 1955-
Aróstegui Gorospe, Juan Ignacio
author_role author
author2 Remesal, Agustín
Mensa Vilaró, Anna
Murías, Sara
Alcobendas, Rosa
González-Roca, Eva
Ruíz Ortiz, Estíbaliz
Antón, Jordi
Iglesias, Estibaliz
Modesto, Consuelo
Comas, David, 1969-
Puig, Anna
Drechsel, Oliver
Ossowski, Stephan
Yagüe, Jordi L.
Merino, Rosa
Estivill, Xavier, 1955-
Aróstegui Gorospe, Juan Ignacio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Disease genetics
Juvenile idiopathic arthritis
topic Disease genetics
Juvenile idiopathic arthritis
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/36963
http://dx.doi.org/10.1038/s41598-019-40874-2
url http://hdl.handle.net/10230/36963
http://dx.doi.org/10.1038/s41598-019-40874-2
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Scientific Reports. 2019;9(1):4579
info:eu-repo/grantAgreement/ES/1PE/SAF2015-68472-C2-1-R
info:eu-repo/grantAgreement/EC/FP7/262055
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
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application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
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