Osteogenesis imperfecta: recent findings shed new light on this once well-understood condition. Genet Med 2009 Jun;11(6):375-85 PMID: 19533842
Pubmed ID
19533842DOI
10.1097/GIM.0b013e3181a1ff7bAbstract
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.
Author List
Basel D, Steiner RDAuthor
Donald Basel MD Chief, Associate Professor in the Pediatrics department at Medical College of WisconsinScopus
2-s2.0-69549096354 84 CitationsMESH terms used to index this publication - Major topics in bold
CollagenCollagen Type I
Genotype
Humans
Models, Biological
Mutation
Osteogenesis Imperfecta
Phenotype
