Osteogenesis imperfecta is a genetic disorder of increased bone fragility and low bone mass. Osteogenesis imperfecta patients present with bone fragility and skeletal deformity within a broad phenotypic range: from a mild (type I) to a lethal form (type II), including two other types presenting varied severity (types III and IV).

Osteogenesis imperfecta is a dominant autosomal disorder caused by mutations in type I collagen genes, COL1A1 and COL1A2, which are responsible for synthesis of this main protein of bones, skin, ligaments, tendons and most other connective tissues. Those genes encode the alpha 1 and alpha 2 chains of the collagen triple helix, respectively.

The severe and lethal forms of osteogenesis imperfecta result from dominant negative mutations in COL1A1 or COL1A2, which produce structural defects in the collagen molecule. The varied clinical characteristics of osteogenesis imperfecta reflect different classes of mutations in different regions of type I collagen genes. Consequently, more than 250 different mutations in the COL1A1 and COL1A2 genes had been characterized. These alterations vary in type and location. The most common in COL1 loci are single-base substitutions in the part of the gene coding for the triple helix domain, which result in replacing glycine by an amino acid with a bulkier side chain.