Mutation analysis of COL1A1 and COL1A2 in patients diagnosed with osteogenesis imperfecta type I-IV

Rebecca Pollitt, Robert McMahon, Janice Nunn, Robert Bamford, Amal Afifi, Nicholas Bishop, Ann Dalton

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Osteogenesis Imperfecta (OI) is a heterogeneous group of inherited disorders characterized by increased bone fragility, with clinical severity ranging from mild to lethal. To date, seven types of OI have been described, based on clinical phenotype and histological findings. Most patients with a clinical diagnosis of OI type I-IV have a mutation in the COL1A1 or COL1A2 genes which encode the two alpha chains of type I collagen, the major component of the bone matrix. Analysis of COL1A1 and COL1A2 in a cohort of 83 unrelated patients with OI type I-IV identified a total of 62 mutations. Thirty-eight appear novel, 26 in COL1A1, and 12 in COL1A2, and these are described here. The largest group consists of point mutations affecting glycine residues in the triple helical domain of the two alpha chains, predicted to disrupt protein folding and structure. This is in accordance with previously published data. A doublet GC deletion, an unusual 398 base deletion predicted to completely remove exon 20 of COL1A2, and a point mutation resulting in substitution of a conserved cysteine in the C-terminal propeptide are described. In addition rare mutations at the cleavage sites of the C-propeptide and the N-terminal signal peptide are described.
Original languageEnglish
Pages (from-to)716
JournalHuman Mutation
Issue number7
Early online date19 Jun 2006
Publication statusPublished - Jul 2006


  • Base Sequence
  • Cohort Studies
  • Collagen
  • Collagen Type I
  • DNA Mutational Analysis
  • Exons
  • Female
  • Humans
  • Male
  • Mutation
  • Osteogenesis Imperfecta
  • Point Mutation
  • Protein Structure, Tertiary
  • Sequence Deletion


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