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2019-03-14

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cc-by (c) Rabionet Janssen, Raquel et al., 2019
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/130852

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

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https://doi.org/10.1038/s41598-019-40874-2

Resum

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.

Matèries

Artritis reumatoide, Joves

Matèries (anglès)

Rheumatoid arthritis, Youth

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Articles publicats en revistes (Genètica, Microbiologia i Estadística)
<b>Publicacions de projectes de recerca finançats per la UE</b>
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

RABIONET JANSSEN, Raquel, REMESAL, Agustín, MENSA-VILARÓ, Anna, MURÍAS, Sara, ALCOBENDAS, Rosa, GONZÁLEZ-ROCA, Eva, RUIZ ORTIZ, Estíbaliz, ANTÓN LÓPEZ, Jordi, IGLESIAS JIMÉNEZ, Estíbaliz, MODESTO, Consuelo, COMAS, David, PUIG, Anna, DRECHSEL, Oliver, OSSOWSKI, Stephan, YAGÜE, Jordi, MERINO, Rosa, ESTIVILL, Xavier, ARÓSTEGUI GOROSPE, Juan ignacio. Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis. _Scientific Reports_. 2019. Vol. 9, núm. 4579. [consulta: 16 de març de 2026]. ISSN: 2045-2322. [Disponible a: https://hdl.handle.net/2445/130852]

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