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Title

Biallelic loss-of-function LACC1/FAMIN Mutations Presenting as Rheumatoid Factor-Negative Polyarticular Juvenile Idiopathic Arthritis

AuthorsRabionet, Raquel; Remesal, Agustín; Mensa-Vilaró, Anna; Murías, Sara; Alcobendas, Rosa; González-Roca, Eva; Ruiz-Ortiz, Estibaliz; Antón, Jordi; Iglesias, Estibaliz; Modesto, Consuelo; Comas, Ddavid; Puig, Anna; Drechsel, Oliver; Ossowski, Stephan; Yagüe, Jordi; Merino, Rosa; Estivill, Xavier; Arostegui, Juan I.
Issue Date14-Mar-2019
PublisherSpringer Nature
CitationScientific Reports 9: 4579 (2019)
AbstractJuvenile 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.
Publisher version (URL)http://doi.org/10.1038/s41598-019-40874-2
URIhttp://hdl.handle.net/10261/207871
Identifiersdoi: 10.1038/s41598-019-40874-2
e-issn: 2045-2322
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