Localization of a structural defect in type I procollagen in a patient affected with the severe non-lethal form of Osteogenesis imperfecta

Ital J Biochem. 1987 Jul-Aug;36(4):256-66.

Abstract

A case of severe non-lethal Osteogenesis imperfecta was studied. The patient's cultured skin fibroblasts synthesised a mixed population of type I collagen chains some of which showed abnormal behaviour on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Further analysis revealed that two types of alpha 1(I) chains were synthesised, both an abnormal, slower migrating and a normal species. A small defect in one allele of one of the type I procollagen chains could lead to the larger size of the abnormal chains, probably caused by overmodifications of the triple helical region. CNBr peptide mapping allowed us to localise the defect midway along the triple helix: the defect site could be assigned to the region between the alpha 1(I)CB-3 and CB-7 peptides. The abnormal alpha 1(I) chains synthesised by the patient's cells had a melting temperature which was about 2 degrees C lower than normal chains. The results appear to be in agreement with the defect localisation and the phenotype.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / analysis
  • Child
  • Collagen / analysis
  • Collagen / biosynthesis
  • Fibroblasts / metabolism*
  • Humans
  • Male
  • Osteogenesis Imperfecta / genetics
  • Osteogenesis Imperfecta / metabolism*
  • Peptide Mapping
  • Procollagen / analysis*
  • Procollagen / biosynthesis
  • Procollagen / genetics

Substances

  • Amino Acids
  • Procollagen
  • Collagen