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. Everts; J. 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

doi:https://doi.org/10.1056/NEJMoa1308223

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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Abstract

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 language	English
Pages (from-to)	1529-1536
Journal	The New England journal of medicine
Volume	369
Issue number	16
DOIs	https://doi.org/10.1056/NEJMoa1308223
Publication status	Published - 2013

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https://doi.org/10.1056/NEJMoa1308223

https://pure.uva.nl/ws/files/1804789/138748_399631.pdf

Cite this

van Dijk, F. S., Zillikens, M. C., Micha, D., Riessland, M., Marcelis, C. L. M., de Die-Smulders, C. E., Milbradt, J., Franken, A. A., Harsevoort, A. J., Lichtenbelt, K. D., Pruijs, H. E., Rubio-Gozalbo, M. E., Zwertbroek, R., Moutaouakil, Y., Egthuijsen, J., Hammerschmidt, M., Bijman, R., Semeins, C. M., Bakker, A. D., ... Pals, G. (2013). PLS3 mutations in X-linked osteoporosis with fractures. The New England journal of medicine, 369(16), 1529-1536. https://doi.org/10.1056/NEJMoa1308223

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title = "PLS3 mutations in X-linked osteoporosis with fractures",

abstract = "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.",

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

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van Dijk, FS, Zillikens, MC, Micha, D, Riessland, M, Marcelis, CLM, de Die-Smulders, CE, Milbradt, J, Franken, AA, Harsevoort, AJ, Lichtenbelt, KD, Pruijs, HE, Rubio-Gozalbo, ME, Zwertbroek, R, Moutaouakil, Y, Egthuijsen, J, Hammerschmidt, M, Bijman, R, Semeins, CM, Bakker, AD, Everts, V, Klein-Nulend, J, Campos-Obando, N, Hofman, A, te Meerman, GJ, Verkerk, AJMH, Uitterlinden, AG, Maugeri, A , Sistermans, EA , Waisfisz, Q , Meijers-Heijboer, H, Wirth, B, Simon, MEH & Pals, G 2013, 'PLS3 mutations in X-linked osteoporosis with fractures', The New England journal of medicine, vol. 369, no. 16, pp. 1529-1536. https://doi.org/10.1056/NEJMoa1308223

TY - JOUR

T1 - PLS3 mutations in X-linked osteoporosis with fractures

AU - van Dijk, F.S.

AU - Zillikens, M.C.

AU - Micha, D.

AU - Riessland, M.

AU - Marcelis, C.L.M.

AU - de Die-Smulders, C.E.

AU - Milbradt, J.

AU - Franken, A.A.

AU - Harsevoort, A.J.

AU - Lichtenbelt, K.D.

AU - Pruijs, H.E.

AU - Rubio-Gozalbo, M.E.

AU - Zwertbroek, R.

AU - Moutaouakil, Y.

AU - Egthuijsen, J.

AU - Hammerschmidt, M.

AU - Bijman, R.

AU - Semeins, C.M.

AU - Bakker, A.D.

AU - Everts, V.

AU - Klein-Nulend, J.

AU - Campos-Obando, N.

AU - Hofman, A.

AU - te Meerman, G.J.

AU - Verkerk, A.J.M.H.

AU - Uitterlinden, A.G.

AU - Maugeri, A.

AU - Sistermans, E.A.

AU - Waisfisz, Q.

AU - Meijers-Heijboer, H.

AU - Wirth, B.

AU - Simon, M.E.H.

AU - Pals, G.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - https://doi.org/10.1056/NEJMoa1308223

DO - https://doi.org/10.1056/NEJMoa1308223

M3 - Article

C2 - 24088043

SN - 0028-4793

VL - 369

SP - 1529

EP - 1536

JO - The New England journal of medicine

JF - The New England journal of medicine

IS - 16

ER -