{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:26:00Z","timestamp":1790807160127,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T00:00:00Z","timestamp":1584403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T00:00:00Z","timestamp":1586822400000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osteogenesis imperfecta (OI) is a primary bone fragility disorder with an estimated prevalence of 1 in 15,000 births. The majority of OI cases are inherited in an autosomal-dominant manner, while 5% to 10% have recessive or X-linked inheritance. Up to now, approximately 5% of OI cases remain without mutation demonstrated, supporting the involvement of other genes in the disease spectrum. By whole-exome sequencing, we identified a homozygous variant (c.2T&amp;gt;C) in CCDC134 gene in three patients from two unrelated families with severe bone fragility that did not respond to bisphosphonate treatment, short stature, and gracile long bones with pseudarthroses but no dentinogenesis imperfecta. CCDC134 encodes a secreted protein widely expressed and implicated in the regulation of some mitogen-activated protein kinases (MAPK) signaling pathway. Western blot and immunofluorescence analyses confirmed the absence of CCDC134 protein in patient cells compared with controls. Furthermore, we demonstrated that CCDC134 mutations are associated with increased Erk1\/2 phosphorylation, decreased OPN mRNA and COL1A1 expression and reduced mineralization in patient osteoblasts compared with controls. These data support that CCDC134 is a new gene involved in severe progressive deforming recessive osteogenesis imperfecta (type III). \u00a9 2020 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.4011","type":"journal-article","created":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T10:34:15Z","timestamp":1584441255000},"page":"1470-1480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta"],"prefix":"10.1093","volume":"35","author":[{"given":"Johanne","family":"Dubail","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics and Reference Centre for Constitutional Bone Diseases INSERM U1163, Universit\u00e9 de Paris, Imagine Institute, Necker-Enfants Malades Hospital, AP-HP F-75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrine","family":"Brunelle","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Reference Centre for Constitutional Bone Diseases INSERM U1163, Universit\u00e9 de Paris, Imagine Institute, Necker-Enfants Malades Hospital, AP-HP F-75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Baujat","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Reference Centre for Constitutional Bone Diseases INSERM U1163, Universit\u00e9 de Paris, Imagine Institute, Necker-Enfants Malades Hospital, AP-HP F-75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Huber","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Reference Centre for Constitutional Bone Diseases INSERM U1163, Universit\u00e9 de Paris, Imagine Institute, Necker-Enfants Malades Hospital, AP-HP F-75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Doyard","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Reference Centre for Constitutional Bone Diseases INSERM U1163, Universit\u00e9 de Paris, Imagine Institute, Necker-Enfants Malades Hospital, AP-HP F-75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Michot","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Reference Centre for Constitutional Bone Diseases INSERM U1163, Universit\u00e9 de Paris, Imagine Institute, Necker-Enfants Malades Hospital, AP-HP F-75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5128-7361","authenticated-orcid":false,"given":"Pascale","family":"Chavassieux","sequence":"additional","affiliation":[{"name":"INSERM UMR 1033, Universit\u00e9 de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdeslam","family":"Khairouni","sequence":"additional","affiliation":[{"name":"Pediatric Orthopedics Casablanca Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicken","family":"Topouchian","sequence":"additional","affiliation":[{"name":"Pediatrics Orthopedics Department, Necker-Enfants Malade Hospital Paris Descartes University, Assistance Publique-H\u00f4pitaux de Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Monnot","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Reference Centre for Constitutional Bone Diseases INSERM U1163, Universit\u00e9 de Paris, Imagine Institute, Necker-Enfants Malades Hospital, AP-HP F-75015 Paris 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