Mutations in WNT1 cause different forms of bone fragility
We report that hypofunctional alleles of WNT1 cause autosomal-recessive osteogenesis imperfecta, a congenital disorder characterized by reduced bone mass and recurrent fractures. In consanguineous families, we identified five homozygous mutations in WNT1: one frameshift mutation, two missense mutati...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
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Cell Press
2013
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| Online Access: | http://hdl.handle.net/20.500.11937/66753 |
| _version_ | 1848761384684224512 |
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| author | Keupp, K. Beleggia, F. Kayserili, H. Barnes, A. Steiner, M. Semler, O. Fischer, B. Yigit, G. Janda, C. Becker, J. Breer, S. Altunoglu, U. Grünhagen, J. Krawitz, P. Hecht, J. Schinke, T. Makareeva, E. Lausch, E. Cankaya, T. Caparrós-Martín, Jose Lapunzina, P. Temtamy, S. Aglan, M. Zabel, B. Eysel, P. Koerber, F. Leikin, S. Garcia, K. Netzer, C. Schönau, E. Ruiz-Perez, V. Mundlos, S. Amling, M. Kornak, U. Marini, J. Wollnik, B. |
| author_facet | Keupp, K. Beleggia, F. Kayserili, H. Barnes, A. Steiner, M. Semler, O. Fischer, B. Yigit, G. Janda, C. Becker, J. Breer, S. Altunoglu, U. Grünhagen, J. Krawitz, P. Hecht, J. Schinke, T. Makareeva, E. Lausch, E. Cankaya, T. Caparrós-Martín, Jose Lapunzina, P. Temtamy, S. Aglan, M. Zabel, B. Eysel, P. Koerber, F. Leikin, S. Garcia, K. Netzer, C. Schönau, E. Ruiz-Perez, V. Mundlos, S. Amling, M. Kornak, U. Marini, J. Wollnik, B. |
| author_sort | Keupp, K. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | We report that hypofunctional alleles of WNT1 cause autosomal-recessive osteogenesis imperfecta, a congenital disorder characterized by reduced bone mass and recurrent fractures. In consanguineous families, we identified five homozygous mutations in WNT1: one frameshift mutation, two missense mutations, one splice-site mutation, and one nonsense mutation. In addition, in a family affected by dominantly inherited early-onset osteoporosis, a heterozygous WNT1 missense mutation was identified in affected individuals. Initial functional analysis revealed that altered WNT1 proteins fail to activate canonical LRP5-mediated WNT-regulated ß-catenin signaling. Furthermore, osteoblasts cultured in vitro showed enhanced Wnt1 expression with advancing differentiation, indicating a role of WNT1 in osteoblast function and bone development. Our finding that homozygous and heterozygous variants in WNT1 predispose to low-bone-mass phenotypes might advance the development of more effective therapeutic strategies for congenital forms of bone fragility, as well as for common forms of age-related osteoporosis. © 2013 The American Society of Human Genetics. |
| first_indexed | 2025-11-14T10:30:49Z |
| format | Journal Article |
| id | curtin-20.500.11937-66753 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:30:49Z |
| publishDate | 2013 |
| publisher | Cell Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-667532018-05-18T08:04:14Z Mutations in WNT1 cause different forms of bone fragility Keupp, K. Beleggia, F. Kayserili, H. Barnes, A. Steiner, M. Semler, O. Fischer, B. Yigit, G. Janda, C. Becker, J. Breer, S. Altunoglu, U. Grünhagen, J. Krawitz, P. Hecht, J. Schinke, T. Makareeva, E. Lausch, E. Cankaya, T. Caparrós-Martín, Jose Lapunzina, P. Temtamy, S. Aglan, M. Zabel, B. Eysel, P. Koerber, F. Leikin, S. Garcia, K. Netzer, C. Schönau, E. Ruiz-Perez, V. Mundlos, S. Amling, M. Kornak, U. Marini, J. Wollnik, B. We report that hypofunctional alleles of WNT1 cause autosomal-recessive osteogenesis imperfecta, a congenital disorder characterized by reduced bone mass and recurrent fractures. In consanguineous families, we identified five homozygous mutations in WNT1: one frameshift mutation, two missense mutations, one splice-site mutation, and one nonsense mutation. In addition, in a family affected by dominantly inherited early-onset osteoporosis, a heterozygous WNT1 missense mutation was identified in affected individuals. Initial functional analysis revealed that altered WNT1 proteins fail to activate canonical LRP5-mediated WNT-regulated ß-catenin signaling. Furthermore, osteoblasts cultured in vitro showed enhanced Wnt1 expression with advancing differentiation, indicating a role of WNT1 in osteoblast function and bone development. Our finding that homozygous and heterozygous variants in WNT1 predispose to low-bone-mass phenotypes might advance the development of more effective therapeutic strategies for congenital forms of bone fragility, as well as for common forms of age-related osteoporosis. © 2013 The American Society of Human Genetics. 2013 Journal Article http://hdl.handle.net/20.500.11937/66753 10.1016/j.ajhg.2013.02.010 Cell Press restricted |
| spellingShingle | Keupp, K. Beleggia, F. Kayserili, H. Barnes, A. Steiner, M. Semler, O. Fischer, B. Yigit, G. Janda, C. Becker, J. Breer, S. Altunoglu, U. Grünhagen, J. Krawitz, P. Hecht, J. Schinke, T. Makareeva, E. Lausch, E. Cankaya, T. Caparrós-Martín, Jose Lapunzina, P. Temtamy, S. Aglan, M. Zabel, B. Eysel, P. Koerber, F. Leikin, S. Garcia, K. Netzer, C. Schönau, E. Ruiz-Perez, V. Mundlos, S. Amling, M. Kornak, U. Marini, J. Wollnik, B. Mutations in WNT1 cause different forms of bone fragility |
| title | Mutations in WNT1 cause different forms of bone fragility |
| title_full | Mutations in WNT1 cause different forms of bone fragility |
| title_fullStr | Mutations in WNT1 cause different forms of bone fragility |
| title_full_unstemmed | Mutations in WNT1 cause different forms of bone fragility |
| title_short | Mutations in WNT1 cause different forms of bone fragility |
| title_sort | mutations in wnt1 cause different forms of bone fragility |
| url | http://hdl.handle.net/20.500.11937/66753 |