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.

De Ridder, Raphaël;Vandeweyer, Geert;Boudin, Eveline;Hendrickx, Gretl;Van Hul, Wim;et.al.
(2021) Calcified Tissue International — Vol. 109, n° 6, p. 656-665 (2021)

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Authors
  • De Ridder, Raphaël
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  • Vandeweyer, Geert
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  • Boudin, Eveline
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  • Hendrickx, Gretl
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  • Devogelaer, Jean-Pierreorcid-logoUCLouvain
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  • Van Hul, Wimorcid-logo
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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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De Ridder, R., Vandeweyer, G., Boudin, E., Hendrickx, G., Huybrechts, Y., Cremers, T. C., Devogelaer, J.-P., Mortier, G., Fransen, E., & Van Hul, W. (2021). 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. Calcified Tissue International, 109(6), 656-665. https://doi.org/10.1007/s00223-021-00881-w (Original work published 2021)