{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:42:23Z","timestamp":1790401343829,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T00:00:00Z","timestamp":1509926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European program SFP7 Sybil"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Genetic determinants contribute to osteoporosis and enhance the risk of fracture. Genomewide association studies of unselected population\u2010based individuals or families have identified polymorphisms in several genes related to low bone density, but not in osteoporotic patients with <jats:italic>Z<\/jats:italic>\u2010score\u2009&lt;\u2009\u22122.0 SD with fragility fracture(s). The aim of this study was to determine the causal genes of idiopathic osteoporosis in the adulthood. Also, we used next\u2010generation sequencing of candidate genes in a cohort of 123 young or middle\u2010aged adults with idiopathic osteoporosis. All patients were included if they had a low bone mineral density (<jats:italic>Z<\/jats:italic>\u2010score\u2009&lt;\u2009\u22122 SD), a diagnosis before age 55 years (mean\u2009\u00b1\u2009SD, 48.4\u2009\u00b1\u200910.6 years; mean\u2009\u00b1\u2009SD age at first fracture, 30.4\u2009\u00b1\u200917.4 years) and fracture or not. We found that 11 patients carried rare or novel variants in <jats:italic>COL1A2<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20094), <jats:italic>PLS3<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20092), <jats:italic>WNT1<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20094), or <jats:italic>DKK1<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20091). We showed a high prevalence of pathogenic variants in <jats:italic>LRP5<\/jats:italic>: 22 patients (17.8%) had the p.Val667Met variant, including three at the homozygous level and 16 (13%) carrying a novel or very rare variant. Functional analysis revealed that the <jats:italic>LRP5<\/jats:italic> missense variants resulted in reduced luciferase activity, which indicates reduced activation of canonical WNT signaling. The clinical phenotype of patients carrying causal gene variants was indistinguishable. In conclusion, molecular screening of young osteoporotic adults revealed several variants and could be useful to characterize susceptibility genes for personalizing treatment, in particular for the new anabolic drugs.\u00a9 2017 The Authors. <jats:italic>JBMR Plus<\/jats:italic> is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbm4.10020","type":"journal-article","created":{"date-parts":[[2017,9,27]],"date-time":"2017-09-27T04:19:07Z","timestamp":1506485947000},"page":"12-21","source":"Crossref","is-referenced-by-count":54,"title":["Primary Osteoporosis in Young Adults: Genetic Basis and Identification of Novel Variants in Causal Genes"],"prefix":"10.1093","volume":"2","author":[{"given":"Corinne","family":"Collet","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Genetics Hospital Lariboisiere Paris France"},{"name":"INSERM U1132 University Paris\u2010Diderot Paris 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