Fig. 4.

Patient database records and animal models shed light on phenotypic variability of osteogenesis imperfecta (OI): insights on prognosis and new targets for therapy. OI is a rare disease with variable severity. To understand the complex genotype–phenotype relationship in OI, researchers combine information from human mutation databases, and available zebrafish and murine OI models carrying dominant mutations in collagen I genes to dissect the contributions of extra- and intracellular factors to disease severity. These include non-collagen components of the extracellular matrix, as well as cellular and molecular processes, such as post-translational modifications (PTM), the unfolded protein response (UPR), and autophagy and cytoskeleton dynamics. These research efforts combined to understand phenotypic variability will improve OI prognosis and allow the identification of novel therapeutic targets.