PLS3 mutations in X-linked osteoporosis with fractures

F.S. van Dijk, M.C. Zillikens, D. Micha, M. Riessland, C.L.M. Marcelis, C.E. de Die-Smulders, J. Milbradt, A.A. Franken, A.J. Harsevoort, K.D. Lichtenbelt, H.E. Pruijs, M.E. Rubio-Gozalbo, R. Zwertbroek, Y. Moutaouakil, J. Egthuijsen, M. Hammerschmidt, R. Bijman, C.M. Semeins, A.D. Bakker, V. EvertsJ. Klein-Nulend, N. Campos-Obando, A. Hofman, G.J. te Meerman, A.J.M.H. Verkerk, A.G. Uitterlinden, A. Maugeri, E.A. Sistermans, Q. Waisfisz, H. Meijers-Heijboer, B. Wirth, M.E.H. Simon, G. Pals

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Plastin 3 (PLS3), a protein involved in the formation of filamentous actin (F-actin) bundles, appears to be important in human bone health, on the basis of pathogenic variants in PLS3 in five families with X-linked osteoporosis and osteoporotic fractures that we report here. The bone-regulatory properties of PLS3 were supported by in vivo analyses in zebrafish. Furthermore, in an additional five families (described in less detail) referred for diagnosis or ruling out of osteogenesis imperfecta type I, a rare variant (rs140121121) in PLS3 was found. This variant was also associated with a risk of fracture among elderly heterozygous women that was two times as high as that among noncarriers, which indicates that genetic variation in PLS3 is a novel etiologic factor involved in common, multi-factorial osteoporosis.
Original languageEnglish
Pages (from-to)1529-1536
JournalThe New England journal of medicine
Issue number16
Publication statusPublished - 2013

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