Osteogenesis imperfecta is a systemic heritable disorder of connective tissue 
whose cardinal manifestation is bone fragility. In approximately 90% of 
individuals with osteogenesis imperfecta, mutations in either of the genes 
encoding the pro-alpha1 or pro-alpha2 chains of type I collagen (COL1A1 or 
COL1A2) can be identified. Of those without collagen mutations, a number of them 
will have mutations involving the enzyme complex responsible for 
posttranslational hydroxylation of the position 3 proline residue of COL1A1. Two 
of the genes encoding proteins involved in that enzyme complex, LEPRE1 and 
cartilage-associated protein, when mutated have been shown to cause autosomal 
recessive osteogenesis imperfecta, which has a moderate to severe clinical 
phenotype, often indistinguishable from osteogenesis imperfecta types II or III. 
Mutations in COL1A1 or COL1A2 which result in an abnormal protein still capable 
of forming a triple helix cause a more severe phenotype than mutations that lead 
to decreased collagen production as a result of the dominant negative effect 
mediated by continuous protein turnover. The current standard of care includes a 
multidisciplinary approach with surgical intervention when necessary, proactive 
physiotherapy, and consideration for the use of bisphosphonates all in attempts 
to improve quality of life.