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, Raphaël, Vandeweyer, Geert, Boudin, Eveline, Hendrickx, Gretl, Huybrechts, Yentl, Cremers, Tycho Canter, Devogelaer, Jean-Pierre, Mortier, Geert, Fransen, Erik, Van Hul, Wim
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Zdroj: Calcified Tissue International; Dec2021, Vol. 109 Issue 6, p656-665, 10p
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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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