Six at Sixty. Commentary on osteogenesis imperfecta 1975-2025.

Abstract

Between 1975 and 1977, my collaborators and I conducted a whole-of-population study in Victoria, Australia, examining the various presentations and clinical manifestations of osteogenesis imperfecta (OI) and familial forms of bone fragility. In 1975, the prevailing view was that all presentations of OI reflected variable expression of pathogenic genomic variants at a single gene locus-possibly 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 >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.