Mutational profile of rare variants in inflammasome-related genes in Behçet disease : A Next Generation Sequencing approach
Burillo-Sanz, Sergio (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Montes-Cano, Marco-Antonio (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
García-Lozano, José-Raúl (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Ortiz-Fernández, Lourdes (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Ortego-Centeno, Norberto (Hospital Universitario San Cecilio (Granada))
García-Hernández, Francisco-José (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Espinosa, Gerard (Hospital Universitari Clínic)
Graña-Gil, Genaro (Complejo Hospitalario Universitario de A Coruña)
Sánchez-Bursón, Juan (Hospital Universitario Virgen de Valme (Sevilla, Andalusia))
Juliá, María Rosa (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Solans, Roser (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Blanco, Ricardo (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Barnosi-Marín, Ana-Celia (Complejo Hospitalario Torrecárdenas (Almeria))
Gómez de la Torre, Ricardo (Hospital Universitario Central de Asturias)
Fanlo, Patricia (Hospital Virgen del Camino (Pamplona))
Rodríguez-Carballeira, Mónica (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Rodriguez-Rodriguez, Luis (Hospital Clínico San Carlos (Madrid))
Camps, Teresa (Hospital Regional Universitario de Málaga)
Castañeda, Santos (Instituto de Investigación Hospital Universitario de la Princesa)
Alegre-Sancho, Juan José (Hospital Universitari Doctor Peset (València))
Martín, Javier (Instituto de Parasitología y Biomedicina "López-Neyra")
González-Escribano, María Francisca (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Universitat Autònoma de Barcelona

Date:	2017
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 BDISCIII.
Grants:	Ministerio de Economía y Competitividad PI16/01373 Ministerio de Economía y Competitividad 13/01118
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Scientific reports, Vol. 7 (august 2017) , ISSN 2045-2322

DOI: 10.1038/s41598-017-09164-7
PMID: 28814775

9 p, 1.1 MB

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