Osteogenesis imperfecta, a heritable connective tissue disorder, has four clinical classifications that span from a mild to a lethal perinatal form. Studies in the preceding decades have defined the molecular basis of the disease as involving the type I procollagen genes. Numerous mutations have been identified based on the assumption that the position and type of mutation would reveal the link between genotype and phenotype. However, no single model has arisen that allows phenotypic diagnosis (clinical classification) based on identifying the mutation alone. Recent research indicates that the presence of a type I collagen mutation has pleiotropic effects on cells - altering not only collagen levels but also the levels of noncollagenous extracellular components, inducing error-checking machinery within the cell, and altering cellular proliferation. Defining the molecular mechanisms that give rise to these other effects may provide a better molecular basis for clinical diagnosis and potential therapeutics.
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