Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/130852
Title: Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
Author: Rabionet Janssen, Raquel
Remesal, Agustín
Mensa-Vilaró, Anna
Murías, Sara
Alcobendas, Rosa
González-Roca, Eva
Ruiz-Ortiz, Estíbaliz
Antón, Jordi
Iglesias, Estibaliz
Modesto, Consuelo
Comas, David
Puig, Anna
Drechsel, Oliver
Ossowski, Stephan
Yagüe, Jordi
Merino, Rosa
Estivill, Xavier, 1955-
Aróstegui Gorospe, Juan Ignacio
Keywords: Artritis reumatoide
Joves
Rheumatoid arthritis
Youth
Issue Date: 14-Mar-2019
Publisher: Nature Publishing Group
Abstract: 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.
Note: Reproducció del document publicat a: https://doi.org/10.1038/s41598-019-40874-2
It is part of: Scientific Reports, 2019, vol. 9, p. 4579
URI: http://hdl.handle.net/2445/130852
Related resource: https://doi.org/10.1038/s41598-019-40874-2
ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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