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Title
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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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Author
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Abstract
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| 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-kappa B 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-kappa B signaling in PDB and confirm the association of previously associated genes with the pathogenesis of PDB. |
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Language
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English
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Source (journal)
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Calcified tissue international. - New York, N.Y., 1979, currens
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Publication
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New york
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Springer
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2021
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ISSN
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0171-967X
[print]
1432-0827
[online]
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DOI
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10.1007/S00223-021-00881-W
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Volume/pages
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109
:6
(2021)
, p. 656-665
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ISI
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000666919700002
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Pubmed ID
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34173013
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Full text (Publisher's DOI)
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Full text (open access)
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Full text (publisher's version - intranet only)
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