Recessively inherited forms of osteogenesis imperfecta

Annu Rev Genet. 2012;46:475-97. doi: 10.1146/annurev-genet-110711-155608.


More than 90% of people who have osteogenesis imperfecta (OI) have heterozygous mutations in one of the two type I collagen genes, COL1A1 and COL1A2. The effects of these changes range from death in the perinatal period to barely increased fracture frequency and reflect different types of mutations. Introduction of bisphosphonates during the past 20 years has targeted bone fragility by decreased resorption. The recent recognition of biallelic mutations in genes that affect either collagen assembly and processing or the regulation of osteoblast development has raised hopes for therapies that would be specific for single-gene disorders and identify cellular targets in individuals with the dominant forms of OI. These hopes are yet to be met, but the study of the recessively inherited forms of OI has illuminated the details of the collagen processing pathways.

Publication types

  • Review

MeSH terms

  • Alleles
  • Collagen Type I / genetics
  • Fractures, Bone / genetics*
  • Fractures, Bone / pathology
  • Gene Frequency
  • Genes, Recessive*
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease / genetics
  • Genetics, Population
  • HSP47 Heat-Shock Proteins / genetics
  • HSP47 Heat-Shock Proteins / metabolism
  • Heterozygote
  • Humans
  • Inheritance Patterns*
  • Mutation*
  • Osteogenesis Imperfecta / genetics*
  • Phenotype
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / genetics
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / metabolism
  • Procollagen-Proline Dioxygenase / genetics
  • Procollagen-Proline Dioxygenase / metabolism
  • Tacrolimus Binding Proteins / genetics
  • Tacrolimus Binding Proteins / metabolism


  • Collagen Type I
  • HSP47 Heat-Shock Proteins
  • SERPINH1 protein, human
  • collagen type I, alpha 1 chain
  • Procollagen-Proline Dioxygenase
  • PLOD2 protein, human
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
  • P3H2 protein, human
  • Tacrolimus Binding Proteins
  • FKBP10 protein, human