Mutational profile of rare variants in inflammasome-related genes in Behçet disease: A Next Generation Sequencing approach

Sergio Burillo-Sanz, Marco Antonio Montes-Cano, José Raúl García-Lozano, Lourdes Ortiz-Fernández, Norberto Ortego-Centeno, Francisco José García-Hernández, Gerard Espinosa, Genaro Graña-Gil, Juan Sánchez-Bursón, María Rosa Juliá, Roser Solans, Ricardo Blanco, Ana Celia Barnosi-Marín, Ricardo Gómez De La Torre, Patricia Fanlo, Mónica Rodríguez-Carballeira, Luis Rodríguez-Rodríguez, Teresa Camps, Santos Castañeda, Juan Jose Alegre-SanchoJavier Martín, María Francisca González-Escribano

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Abstract

© 2017 The Author(s). Behçet's disease (BD) is an immune-mediated systemic disorder with a well-established association with HLA class I and other genes. BD has clinical overlap with many autoinflammatory diseases (AIDs). The aim of this study was to investigate the role of rare variants in seven genes involved in AIDs: CECR1, MEFV, MVK, NLRP3, NOD2, PSTPIP1 and TNFRSF1A using a next generation sequencing (NGS) approach in 355 BD patients. To check global association of each gene, 4 tests: SKAT, CollapseBt, C(α) and weighted KBAC were used. Databases: 1000 Genomes Project Phase 3, Infevers, HGMD and ClinVar and algorithms: PolyPhen2 and SIFT were consulted to collect information of the 62 variants found. All the genes resulted associated using SKAT but only 3 (MVK, NOD2 and PSTPIP1) with C(α) and weighted KBAC. When all the genes are considered, 40 variants were associated to AIDs in clinical databases and 25 were predicted as pathogenic at least by one of the algorithms. Including only MVK, NOD2 and PSTPIP1, the associated to AIDs variants found in BD were 20 and the predicted as pathogenic, 12. The maxima contribution corresponds to NOD2. This study supports influence of rare variants in genes involved in AIDs in the pathogenesis of BD.
Original languageEnglish
Article number8453
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

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