A Panel-Based Sequencing Analysis of Patients with Paget's Disease of Bone Suggests Enrichment of Rare Genetic Variation in regulators of NF-κB Signaling and Supports the Importance of the 7q33 Locus.

Autor: De Ridder R; Center of Medical Genetics, University of Antwerp & Antwerp University Hospital, Antwerp, Belgium., Vandeweyer G; Center of Medical Genetics, University of Antwerp & Antwerp University Hospital, Antwerp, Belgium., Boudin E; Center of Medical Genetics, University of Antwerp & Antwerp University Hospital, Antwerp, Belgium., Hendrickx G; Center of Medical Genetics, University of Antwerp & Antwerp University Hospital, Antwerp, Belgium., Huybrechts Y; Center of Medical Genetics, University of Antwerp & Antwerp University Hospital, Antwerp, Belgium., Cremers TC; Center of Medical Genetics, University of Antwerp & Antwerp University Hospital, Antwerp, Belgium., Devogelaer JP; Department of Rheumatology, Saint-Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium., Mortier G; Center of Medical Genetics, University of Antwerp & Antwerp University Hospital, Antwerp, Belgium., Fransen E; Center of Medical Genetics, University of Antwerp & Antwerp University Hospital, Antwerp, Belgium., Van Hul W; Center of Medical Genetics, University of Antwerp & Antwerp University Hospital, Antwerp, Belgium. wim.vanhul@uantwerpen.be.
Jazyk: angličtina
Zdroj: Calcified tissue international [Calcif Tissue Int] 2021 Dec; Vol. 109 (6), pp. 656-665. Date of Electronic Publication: 2021 Jun 25.
DOI: 10.1007/s00223-021-00881-w
Abstrakt: Paget's disease of bone (PDB) is a common bone disorder characterized by focal lesions caused by increased bone turnover. Monogenic forms of PDB and PDB-related phenotypes as well as genome-wide association studies strongly support the involvement of genetic variation in components of the NF-κB signaling pathway in the pathogenesis of PDB. In this study, we performed a panel-based mutation screening of 52 genes. Single variant association testing and a series of gene-based association tests were performed. The former revealed a novel association with NFKBIA and further supports an involvement of variation in NR4A1, VCP, TNFRSF11A, and NUP205. The latter indicated a trend for enrichment of rare genetic variation in GAB2 and PRKCI. Both single variant tests and gene-based tests highlighted two genes, NR4A1 and NUP205. In conclusion, our findings support the involvement of genetic variation in modulators of NF-κB signaling in PDB and confirm the association of previously associated genes with the pathogenesis of PDB.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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