Sillence David
Genomic Medicine, University of Sydney Clinical School, Children's Hospital, Westmead, New South Wales, Australia
J Med Genet. 2025 May 27;62(6):422-426. doi: 10.1136/jmg-2025-110807.
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.
1975年至1977年间，我和我的合作者在澳大利亚维多利亚州开展了一项全人群研究，调查成骨不全症（OI）的各种表现形式以及家族性骨脆性疾病。1975年，普遍观点认为，OI的所有表现都反映了单个基因座上致病基因组变异的可变表达——可能涉及最近发现的I型胶原蛋白。我们得出结论，OI实际上具有遗传异质性，为未来的生化和基因组学发现奠定了基础。目前，人们认识到OI是由20多个基因的病理性变异导致的，许多其他基因座的变异会导致家族性骨质疏松症的相关形式或以骨脆性为特征的特殊综合征。已采用二元疾病分类法来帮助临床医生、研究人员和患者进行OI的诊断、治疗和研究，重点是精准医学。
