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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, 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: 14 de gener de 2026]. ISSN: 2045-2322. [Disponible a: https://hdl.handle.net/2445/130852]

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