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In 1975, the prevailing view was that all presentations of OI reflected variable expression of pathogenic genomic variants at a single gene locus\u2014possibly involving the recently identified protein, type I collagen. We concluded that OI was in fact genetically heterogeneous, setting the scene for future biochemical and genomic discoveries. Currently, OI is recognised to result from pathological variants in &gt;20 genes, with variants in many further loci resulting in related forms of familial osteoporosis or special syndromes characterised by bone fragility. A dyadic nosology has been adopted to help clinicians, researchers and affected individuals in accessing OI diagnosis, treatment and research with a focus on precision medicine.<\/jats:p>","DOI":"10.1136\/jmg-2025-110807","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T11:36:06Z","timestamp":1748345766000},"page":"422-426","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Six at Sixty. Commentary on osteogenesis imperfecta 1975\u20132025"],"prefix":"10.1136","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5638-2998","authenticated-orcid":false,"given":"David","family":"Sillence","sequence":"first","affiliation":[{"name":"Genomic Medicine, University of Sydney Clinical School, Children's Hospital, Westmead, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"2025101715001350000_62.6.422.1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.16.2.101"},{"key":"2025101715001350000_62.6.422.2","unstructured":"Sillence D . Bone dysplasia: genetic and ultrastructural studies with special reference to osteogenesis imperfecta. Ann Arbor, Michigan USA: University Microfilms International, 1980."},{"key":"2025101715001350000_62.6.422.3","unstructured":"McKusick VA . Mendelian inheritance in man: catalogs of autosomal dominant, autosomal recessive, and x-linked phenotypes. 1983."},{"key":"2025101715001350000_62.6.422.4","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1302\/0301-620X.57B1.2","article-title":"A new look at osteogenesis imperfecta. 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