[Osteogenesis Imperfecta - Mutations and Phenotypes]

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited, mostly dominant, disorders characterized by skeletal brittleness. OI generally results from mutations in the genes that encode the al(I) and alpha 2(I) chains; these chains, associated in a triple helix constitute type I collagen. Mutations leading to a purely quantitative defect result in discrete symptoms, compared to those resulting from mutations accompanied by an accumulation of mutated chains. These mutated subunits disturb the conformation of the triple helix and thus the functional properties of collagen fibrils, even in heterozygous patients. The severity of the phenotype depends on the nature of the mutated aminoacid and on its position in the protein; carboxyterminal mutations are usually more severe than aminoterminal mutations, due to the fact that the folding of the constitutive triple helix always starts from the carboxyterminal end of the chains. Moreover, triple helix being composed of two alpha 1 chains and one alpha 2 chain, mutations in alpha 1 chains are generally more deleterious than those occuring in alpha 2 chains.