Osteogenesis imperfecta

Osteogenesis imperfecta (OI) also known as “Brittle Bone Disease” is a clinically heterogeneous heritable connective tissue disorder, the causative defects of which are directly related to type I collagen, including abnormalities of col­lagen primary structure and insufficient protein quan­tity, post-translational modification, folding, intracellular transport or matrix incorporation. More recently altered osteoblasts differentiation and activity have been identified as a cause of OI. The clinical features of osteogenesis imperfecta commonly include low bone mass and reduced bone material strength, which result in bone fragility and susceptibility to fracture in absence of trauma, bone defor­mity and growth deficiency.

In its various types, it occurs in approximately 1 in 15,000–20,000 births, with predominantly autosomal dominant inheritance. Over 1,500 dominant mutations in either COL1A1or COL1A2, which encode the α1(I) and α2(I) of type I collagen, have been identified. Recessive osteogenesis imperfecta with lethal to mod­erate phenotypes is caused by defects in genes whose products interact with type I collagen. Recessive cases have been reported so far with mutations in genes that encode proteins involved in collagen processing (BMP1), in collagen modification (CRTAP, LEPRE1, PPIB, TMEM38B), in collagen folding and cross-linking (SERPINH1, FKBP10, PLOD2), in bone mineralization (IFITM5, SERPINF1), and in osteoblast development, these latter associated with collagen insufficiency (SP7, WNT1, and CREB3L1).