title: Osteogenesis imperfecta: recent findings shed new light on this once well-understood condition.
abstract: 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.
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon 97239, USA. baseld@ohsu.edu
authors.forename: Donald
authors.initials: D
authors.lastname: Basel
authors.forename: Robert D
authors.initials: RD
authors.lastname: Steiner
mesh_terms: D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D005838:Genotype; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D003094:Collagen