{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:09:28Z","timestamp":1790611768748,"version":"4.1.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    Osteogenesis imperfecta (OI) is a rare inherited connective tissue dysplasia characterized with skeletal fragility, recurrent fractures and bone deformity, predominantly caused by mutations in the genes\n                    <jats:italic>COL1A1<\/jats:italic>\n                    or\n                    <jats:italic>COL1A2<\/jats:italic>\n                    that encode the chains of type I collagen. In the present study, clinical manifestations and genetic variants were analysed from 187 Chinese OI patients, majority of whom are of southern Chinese origin. By targeted sequencing, 63 and 58 OI patients were found carrying mutations in\n                    <jats:italic>COL1A1<\/jats:italic>\n                    and\n                    <jats:italic>COL1A2<\/jats:italic>\n                    respectively, including 8 novel\n                    <jats:italic>COL1A1<\/jats:italic>\n                    and 7 novel\n                    <jats:italic>COL1A2<\/jats:italic>\n                    variants. We validated a novel splicing mutation in\n                    <jats:italic>COL1A1<\/jats:italic>\n                    . A diverse mutational and phenotypic spectrum was observed, coupling with the heterogeneity observed in the transcriptomic data derived from osteoblasts of six patients from our cohort. Missense mutations were significantly associated (\u03c7\n                    <jats:sup>2<\/jats:sup>\n                    <jats:italic>p<\/jats:italic>\n                    = 0.0096) with a cluster of patients with more severe clinical phenotypes. Additionally, the severity of OI was more correlated with the quality of bones, rather than the bone mineral density. Bone density is most responsive to bisphosphonate treatment during the juvenile stage (10\u201315 years old). In contrast, height is not responsive to bisphosphonate treatment. Our findings expand the mutational spectrum of type I collagen genes and the genotype-phenotype correlation in Chinese OI patients. The observation of effective bisphosphonate treatment in an age-specific manner may help to improve OI patient management.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2022.816078","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T03:09:59Z","timestamp":1643339399000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Phenotypic Spectrum and Molecular Basis in a Chinese Cohort of Osteogenesis Imperfecta With Mutations in Type I Collagen"],"prefix":"10.3389","volume":"13","author":[{"given":"Peikai","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijia","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiu Tung","family":"Shek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-nan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yapeng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxin","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anmei","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Kai Tsun","family":"To","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1172\/jci200419900","article-title":"PPAR \u03b3 Insufficiency Enhances Osteogenesis through Osteoblast Formation from Bone Marrow Progenitors","volume":"113","author":"Akune","year":"2004","journal-title":"J. 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