{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:18:33Z","timestamp":1789359513171,"version":"build-2803163510"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2005,11,1]],"date-time":"2005-11-01T00:00:00Z","timestamp":1130803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We studied whether the LRP5 gene contributes to the clinical phenotype of IO in men. Mutation analysis in 66 IO men revealed a range of sequence variants, of which two missense variants were shown to be of functional relevance.<\/jats:p>\n               <jats:p>Introduction: Mutations in the LDL receptor-related protein 5 (LRP5) gene have been associated with extreme bone phenotypes, which makes LRP5 a plausible candidate gene for idiopathic osteoporosis (IO).<\/jats:p>\n               <jats:p>Materials and Methods: In 66 men with IO, all 23 exons and exon-intron boundaries of the LRP5 gene were screened for mutations, and functional analyses were performed for those that were putatively involved in the phenotype.<\/jats:p>\n               <jats:p>Results: Mutation analysis in the IO probands revealed five missense mutations, of which 1067C&amp;gt;T (S356L), 1364C&amp;gt;T (S455L), and 4609G&amp;gt;A (A1537T) were of potential functional significance because they were located in highly conserved regions of LRP5 and not found in a control panel. Segregation analysis in the respective families could not exclude their possible causality for IO. Furthermore, functional analyses clearly showed an inhibitory effect of mutations 1067C&amp;gt;T and 1364C&amp;gt;T on Wnt signal transduction. These effects are most likely caused by impaired LRP5 synthesis in the case of 1067C&amp;gt;T and failure of protein trafficking to the cell surface for 1364C&amp;gt;T.<\/jats:p>\n               <jats:p>Conclusions: For 2 of 66 IO probands, a mutation in the LRP5 gene with proven functionality was found. The findings indicate that carrying an LRP5 mutation is a risk factor for IO, but that overall, IO in men is infrequently underlied by such a mutation.<\/jats:p>","DOI":"10.1359\/jbmr.050705","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T07:27:46Z","timestamp":1146122866000},"page":"1951-1959","source":"Crossref","is-referenced-by-count":26,"title":["Missense Mutations in <i>LRP5<\/i> Are Not a Common Cause of Idiopathic Osteoporosis in Adult Men"],"prefix":"10.1093","volume":"20","author":[{"given":"Patricia","family":"Crabbe","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Ghent University Hospital, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Balemans","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University and University Hospital of Antwerp, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Willaert","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ghent University Hospital, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Van Pottelbergh","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Ghent University Hospital, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erna","family":"Cleiren","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University and University Hospital of Antwerp, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Coucke","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ghent University Hospital, Ghent, 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