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25.06.2021 | Original Research

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

verfasst von: Raphaël De Ridder, Geert Vandeweyer, Eveline Boudin, Gretl Hendrickx, Yentl Huybrechts, Tycho Canter Cremers, Jean-Pierre Devogelaer, Geert Mortier, Erik Fransen, Wim Van Hul

Erschienen in: Calcified Tissue International | Ausgabe 6/2021

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Abstract

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.

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Titel: 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
verfasst von: Raphaël De Ridder
Geert Vandeweyer
Eveline Boudin
Gretl Hendrickx
Yentl Huybrechts
Tycho Canter Cremers
Jean-Pierre Devogelaer
Geert Mortier
Erik Fransen
Wim Van Hul
Publikationsdatum: 25.06.2021
Verlag: Springer US
Erschienen in: Calcified Tissue International / Ausgabe 6/2021
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-021-00881-w

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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

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