Mutational profile of rare variants in inflammasome-related genes in Behçet disease: A Next Generation Sequencing approach
Abstract 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...
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oai:doaj.org-article:a17410930c33440f8760e7431d185c482021-12-02T15:05:04ZMutational profile of rare variants in inflammasome-related genes in Behçet disease: A Next Generation Sequencing approach10.1038/s41598-017-09164-72045-2322https://doaj.org/article/a17410930c33440f8760e7431d185c482017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09164-7https://doaj.org/toc/2045-2322Abstract 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.Sergio Burillo-SanzMarco-Antonio Montes-CanoJosé-Raúl García-LozanoLourdes Ortiz-FernándezNorberto Ortego-CentenoFrancisco-José García-HernándezGerard EspinosaGenaro Graña-GilJuan Sánchez-BursónMaría Rosa JuliáRoser SolansRicardo BlancoAna-Celia Barnosi-MarínRicardo Gómez De la TorrePatricia FanloMónica Rodríguez-CarballeiraLuis Rodríguez-RodríguezTeresa CampsSantos CastañedaJuan-Jose Alegre-SanchoJavier MartínMaría Francisca González-EscribanoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017) |
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Medicine R Science Q 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-Sancho Javier Martín María Francisca González-Escribano Mutational profile of rare variants in inflammasome-related genes in Behçet disease: A Next Generation Sequencing approach |
| description |
Abstract 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. |
| format |
article |
| author |
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-Sancho Javier Martín María Francisca González-Escribano |
| author_facet |
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-Sancho Javier Martín María Francisca González-Escribano |
| author_sort |
Sergio Burillo-Sanz |
| title |
Mutational profile of rare variants in inflammasome-related genes in Behçet disease: A Next Generation Sequencing approach |
| title_short |
Mutational profile of rare variants in inflammasome-related genes in Behçet disease: A Next Generation Sequencing approach |
| title_full |
Mutational profile of rare variants in inflammasome-related genes in Behçet disease: A Next Generation Sequencing approach |
| title_fullStr |
Mutational profile of rare variants in inflammasome-related genes in Behçet disease: A Next Generation Sequencing approach |
| title_full_unstemmed |
Mutational profile of rare variants in inflammasome-related genes in Behçet disease: A Next Generation Sequencing approach |
| title_sort |
mutational profile of rare variants in inflammasome-related genes in behçet disease: a next generation sequencing approach |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/a17410930c33440f8760e7431d185c48 |
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