PLS3 Mutations in X-Linked Osteoporosis with Fractures

Fleur S van Dijk; M Carola Zillikens; Dimitra Micha; Markus Riessland; Carlo L M Marcelis; Christine E de Die-Smulders; Janine Milbradt; Anton A Franken; Arjan J Harsevoort; Klaske D Lichtenbelt; Hans E Pruijs; M Estela Rubio-Gozalbo; Rolf Zwertbroek; Youssef Moutaouakil; Jaqueline Egthuijsen; Matthias Hammerschmidt; Renate Bijman; Cor M Semeins; Astrid D Bakker; Vincent Everts; Jenneke Klein-Nulend; Natalia Campos-Obando; Albert Hofman; Gerard J te Meerman; Annemieke J M H Verkerk; André G Uitterlinden; Alessandra Maugeri; Erik A Sistermans; Quinten Waisfisz; Hanne Meijers-Heijboer; Brunhilde Wirth; Marleen E H Simon; Gerard Pals

doi:10.1056/NEJMoa1308223

PLS3 Mutations in X-Linked Osteoporosis with Fractures

Fleur S van Dijk, M Carola Zillikens, Dimitra Micha, Markus Riessland, Carlo L M Marcelis, Christine E de Die-Smulders, Janine Milbradt, Anton A Franken, Arjan J Harsevoort, Klaske D Lichtenbelt, Hans E Pruijs, M Estela Rubio-Gozalbo, Rolf Zwertbroek, Youssef Moutaouakil, Jaqueline Egthuijsen, Matthias Hammerschmidt, Renate Bijman, Cor M Semeins, Astrid D Bakker, Vincent EvertsJenneke Klein-Nulend, Natalia Campos-Obando, Albert Hofman, Gerard J te Meerman, Annemieke J M H Verkerk, André G Uitterlinden, Alessandra Maugeri, Erik A Sistermans, Quinten Waisfisz, Hanne Meijers-Heijboer, Brunhilde Wirth, Marleen E H Simon, Gerard Pals^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

175 Citations (Scopus)

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
Number of pages	8
Journal	New England Journal of Medicine
Volume	369
Issue number	16
Early online date	2 Oct 2013
DOIs	https://doi.org/10.1056/NEJMoa1308223
Publication status	Published - 17 Oct 2013

Bibliographical note

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EMC MM-01-39-02
EMC MM-01-39-09-A

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http://hdl.handle.net/1765/63409

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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. 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}, {Fleur S} and Zillikens, {M Carola} and Dimitra Micha and Markus Riessland and Marcelis, {Carlo L M} and {de Die-Smulders}, {Christine E} and Janine Milbradt and Franken, {Anton A} and Harsevoort, {Arjan J} and Lichtenbelt, {Klaske D} and Pruijs, {Hans E} and Rubio-Gozalbo, {M Estela} and Rolf Zwertbroek and Youssef Moutaouakil and Jaqueline Egthuijsen and Matthias Hammerschmidt and Renate Bijman and Semeins, {Cor M} and Bakker, {Astrid D} and Vincent Everts and Jenneke Klein-Nulend and Natalia Campos-Obando and Albert Hofman and {te Meerman}, {Gerard J} and Verkerk, {Annemieke J M H} and Uitterlinden, {Andr{\'e} G} and Alessandra Maugeri and Sistermans, {Erik A} and Quinten Waisfisz and Hanne Meijers-Heijboer and Brunhilde Wirth and Simon, {Marleen E H} and Gerard Pals",

note = "Copyright {\textcopyright} 2013 Massachusetts Medical Society.",

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day = "17",

doi = "10.1056/NEJMoa1308223",

language = "English",

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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', 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, Fleur S

AU - Zillikens, M Carola

AU - Micha, Dimitra

AU - Riessland, Markus

AU - Marcelis, Carlo L M

AU - de Die-Smulders, Christine E

AU - Milbradt, Janine

AU - Franken, Anton A

AU - Harsevoort, Arjan J

AU - Lichtenbelt, Klaske D

AU - Pruijs, Hans E

AU - Rubio-Gozalbo, M Estela

AU - Zwertbroek, Rolf

AU - Moutaouakil, Youssef

AU - Egthuijsen, Jaqueline

AU - Hammerschmidt, Matthias

AU - Bijman, Renate

AU - Semeins, Cor M

AU - Bakker, Astrid D

AU - Everts, Vincent

AU - Klein-Nulend, Jenneke

AU - Campos-Obando, Natalia

AU - Hofman, Albert

AU - te Meerman, Gerard J

AU - Verkerk, Annemieke J M H

AU - Uitterlinden, André G

AU - Maugeri, Alessandra

AU - Sistermans, Erik A

AU - Waisfisz, Quinten

AU - Meijers-Heijboer, Hanne

AU - Wirth, Brunhilde

AU - Simon, Marleen E H

AU - Pals, Gerard

PY - 2013/10/17

Y1 - 2013/10/17

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 - 10.1056/NEJMoa1308223

DO - 10.1056/NEJMoa1308223

M3 - Article

C2 - 24088043

SN - 0028-4793

VL - 369

SP - 1529

EP - 1536

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 16

ER -

PLS3 Mutations in X-Linked Osteoporosis with Fractures

Abstract

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