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dc.contributor.author | Rabionet Janssen, 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 | Ruiz Ortiz, Estíbaliz |
dc.contributor.author | Antón, Jordi |
dc.contributor.author | Iglesias Jiménez, Estíbaliz |
dc.contributor.author | Modesto, Consuelo |
dc.contributor.author | Comas, David |
dc.contributor.author | Puig, Anna |
dc.contributor.author | Drechsel, Oliver |
dc.contributor.author | Ossowski, Stephan |
dc.contributor.author | Yagüe, Jordi |
dc.contributor.author | Merino, Rosa |
dc.contributor.author | Estivill, Xavier, 1955- |
dc.contributor.author | Aróstegui Gorospe, Juan Ignacio |
dc.date | 2019-03-25T16:07:51Z |
dc.date | 2019-03-25T16:07:51Z |
dc.date | 2019-03-14 |
dc.date | 2019-03-25T16:07:51Z |
dc.identifier | 2045-2322 |
dc.identifier | 689332 |
dc.identifier | 30872671 |
dc.identifier.uri | http://hdl.handle.net/2445/130852 |
dc.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. |
dc.format | 6 p. |
dc.format | application/pdf |
dc.language | eng |
dc.publisher | Nature Publishing Group |
dc.relation | Reproducció del document publicat a: https://doi.org/10.1038/s41598-019-40874-2 |
dc.relation | Scientific Reports, 2019, vol. 9, p. 4579 |
dc.relation | https://doi.org/10.1038/s41598-019-40874-2 |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/262055/EU//ESGI |
dc.rights | cc-by (c) Rabionet Janssen, Raquel et al., 2019 |
dc.rights | http://creativecommons.org/licenses/by/3.0/es |
dc.rights | info:eu-repo/semantics/openAccess |
dc.subject | Artritis reumatoide |
dc.subject | Joves |
dc.subject | Rheumatoid arthritis |
dc.subject | Youth |
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 | info:eu-repo/semantics/publishedVersion |