Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Mutations in WNT1 cause different forms of bone fragility
American Journal of Human Genetics, Volume 92, No. 4, Year 2013
Notification
URL copied to clipboard!
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 β-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.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3617378/bin/mmc1.pdf
Authors & Co-Authors
Keupp, Katharina
Germany, Koln
Uniklinik Köln
Germany, Koln
Universität zu Köln
Beleggia, Filippo
Germany, Koln
Uniklinik Köln
Germany, Koln
Universität zu Köln
Kayserili, Hülya U.
Turkey, Istanbul
İstanbul Tıp Fakültesi
Barnes, Aileen M.
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Steiner, Magdalena
Germany, Berlin
Charité – Universitätsmedizin Berlin
Semler, Oliver
Germany, Koln
Universität zu Köln
Fischer, Björn
Germany, Berlin
Charité – Universitätsmedizin Berlin
Yigit, Gökhan
Germany, Koln
Uniklinik Köln
Germany, Koln
Universität zu Köln
Janda, Claudia Y.
United States, Stanford
Stanford University School of Medicine
Becker, Jutta
Germany, Koln
Uniklinik Köln
Breer, Stephan
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Altunoğlu, Umut
Turkey, Istanbul
İstanbul Tıp Fakültesi
Grünhagen, Johannes
Germany, Berlin
Charité – Universitätsmedizin Berlin
Krawitz, Peter Michael
Germany, Berlin
Charité – Universitätsmedizin Berlin
Hecht, Jochen
Germany, Berlin
Berlin-brandenburg School for Regenerative Therapies
Schinke, Thorsten
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Makareeva, Elena N.
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Lausch, Ekkehart U.
Germany, Freiburg Im Breisgau
Universität Freiburg
Çankaya, Tufan
Turkey, Izmir
Dokuz Eylül Üniversitesi
Caparros-Martin, José A.
Spain, Madrid
Consejo Superior de Investigaciones Científicas
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Raras
Lapunzina-Badía, Pablo Daniel
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Raras
Spain, Madrid
Hospital Universitario la Paz
Temtamy, Samia Ali Li
Egypt, Giza
National Research Centre
Aglan, Mona Sabry
Egypt, Giza
National Research Centre
Zabel, Bernhard Ulrich
Germany, Freiburg Im Breisgau
Universität Freiburg
Eysel, Peer
Germany, Koln
Universität zu Köln
Koerber, Friederike
Germany, Koln
Universität zu Köln
Leikin, Sergey
United States, Bethesda
National Institute of Child Health and Human Development Nichd
García, Khristofer Christopher
United States, Stanford
Stanford University School of Medicine
Netzer, Christian
Germany, Koln
Uniklinik Köln
Schöenau, Eckhard
Germany, Koln
Universität zu Köln
Ruiz-Perez, Victor L.
Spain, Madrid
Consejo Superior de Investigaciones Científicas
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Raras
Mundlos, Stefan
Germany, Berlin
Charité – Universitätsmedizin Berlin
Germany, Berlin
Max Planck Institute for Molecular Genetics
Amling, Michael
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Kornak, Uwe
Germany, Berlin
Charité – Universitätsmedizin Berlin
Germany, Berlin
Max Planck Institute for Molecular Genetics
Marini, Joan C.Bodurtha
United States, Bethesda
National Institute of Child Health and Human Development Nichd
Wollnik, Bernd
Germany, Koln
Uniklinik Köln
Germany, Koln
Universität zu Köln
Statistics
Citations: 245
Authors: 36
Affiliations: 15
Identifiers
Doi:
10.1016/j.ajhg.2013.02.010
ISSN:
00029297
e-ISSN:
15376605
Research Areas
Cancer
Genetics And Genomics
Noncommunicable Diseases
Violence And Injury