{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:58:31Z","timestamp":1793278711373,"version":"4.5.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-18-CE14-0040"],"award-info":[{"award-number":["ANR-18-CE14-0040"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["16963"],"award-info":[{"award-number":["16963"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chondrodysplasias with multiple dislocations are rare skeletal disorders characterized by hyperlaxity, joint dislocations, and growth retardation. Chondrodysplasias with multiple dislocations have been linked to pathogenic variants in genes encoding proteins involved in the proteoglycan (PG) biosynthesis. In this study, by exome sequencing analysis, we identified a homozygous nonsense variant (NM_001297654.2: c.1825C&amp;gt;T, p.Arg609*) in the discoidin domain receptor 1 (DDR1) gene in a patient presenting joint dislocations, hyperlaxity, and cerebellar hypoplasia. Functional studies revealed decreased PG production in patient fibroblasts. We further demonstrated that DDR1 inhibition impaired the Indian Hedgehog signaling pathway in chondrocytes, decreased differentiation and mineralization in osteoblasts, and disrupted p38 MAPK signaling in both cell types. Additionally, we showed that DDR1 inhibition affected the noncanonical WNT signaling pathway in human skeletal cells and decreased PG production in chondrocytes. These findings suggest that DDR1 is a new gene involved in the group of chondrodysplasias with multiple dislocations and highlights its essential role in human skeletal and brain development.<\/jats:p>","DOI":"10.1093\/jbmr\/zjae205","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T14:29:26Z","timestamp":1734964166000},"page":"362-371","source":"Crossref","is-referenced-by-count":2,"title":["Loss-of-function of <i>DDR1<\/i> is responsible for a chondrodysplasia with multiple dislocations"],"prefix":"10.1093","volume":"40","author":[{"given":"Miriam","family":"Villegas Villarroel","sequence":"first","affiliation":[{"name":"Reference Center for Skeletal Dysplasia, INSERM UMR 1163, Paris Cit\u00e9 University, Imagine Institute, Necker Enfants Malades Hospital (AP-HP) , 75015 Paris 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