Osteogenesis imperfecta: recent findings shed new light on this once well-understood condition

Genet Med. 2009 Jun;11(6):375-85. doi: 10.1097/GIM.0b013e3181a1ff7b.

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.

Publication types

  • Review

MeSH terms

  • Collagen / genetics*
  • Collagen / metabolism
  • Collagen Type I / genetics*
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Genotype
  • Humans
  • Models, Biological
  • Mutation*
  • Osteogenesis Imperfecta / classification
  • Osteogenesis Imperfecta / genetics*
  • Osteogenesis Imperfecta / pathology*
  • Phenotype

Substances

  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Collagen