Section on Heritable Disorders of Bone and Extracellular Matrix, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Section on Adolescent Bone and Body Composition, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Calcif Tissue Int. 2024 Dec;115(6):891-914. doi: 10.1007/s00223-024-01266-5. Epub 2024 Aug 11.
Osteogenesis imperfecta (OI) is a heterogeneous heritable skeletal dysplasia characterized by bone fragility and deformity, growth deficiency, and other secondary connective tissue defects. OI is now understood as a collagen-related disorder caused by defects of genes whose protein products interact with collagen for folding, post-translational modification, processing and trafficking, affecting bone mineralization and osteoblast differentiation. This review provides the latest updates on genetics of OI, including new developments in both dominant and rare OI forms, as well as the signaling pathways involved in OI pathophysiology. There is a special emphasis on discoveries of recessive mutations in TENT5A, MESD, KDELR2 and CCDC134 whose causality of OI types XIX, XX, XXI and XXI, respectively, is now established and expends the complexity of mechanisms underlying OI to overlap LRP5/6 and MAPK/ERK pathways. We also review in detail new discoveries connecting the known OI types to each other, which may underlie an eventual understanding of a final common pathway in OI cellular and bone biology.
成骨不全症（OI）是一种异质性遗传性骨骼发育不良，其特征为骨骼脆弱和畸形、生长发育不良以及其他继发性结缔组织缺陷。OI 现在被理解为一种胶原相关疾病，由其蛋白产物与胶原相互作用以进行折叠、翻译后修饰、加工和运输的基因缺陷引起，影响骨矿化和成骨细胞分化。本综述提供了 OI 遗传学的最新更新，包括显性和罕见 OI 形式的新进展，以及参与 OI 病理生理学的信号通路。特别强调了 TENT5A、MESD、KDELR2 和 CCDC134 中的隐性突变的发现，其分别导致 OI 类型 XIX、XX、XXI 和 XXI，其因果关系现在已经确立，并扩展了 OI 潜在机制的复杂性，与 LRP5/6 和 MAPK/ERK 通路重叠。我们还详细回顾了将已知 OI 类型相互连接的新发现，这可能是最终理解 OI 细胞和骨骼生物学中最终共同途径的基础。
