A cysteine for glycine substitution at position 175 in an α1 (i) chain of type I collagen produces a clinically heterogeneous form of osteogenesis imperfecta

Mary K. Wirtz, Velidi H. Rao, Robert W. Glanville, Michael E. Labhard, Petrus J. Pretorius, W. Nancy de Vries, Wouter J. de Wet, David W. Hollister

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The molecular basis for Osteogenesis Imperfecta in a large kindred with a highly variable phenotype was identified by sequencing the mutant pro α 1 (I) protein, cDNA and genomic DNA from the proband. Fibroblasts from different affected individuals all synthesize both normal Type I procollagen molecules and abnormal Type I procollagen molecules in which one or both proα 1(I) chain(s) contain a cy steine residue within the triple helical domain. Protein studies of the proband localized the mutant cysteine residue to the α 1 (I) CB 8 peptide.1 We now report that cysteine has replaced glycine at triple helical residue 175 disrupting the invariant Gly-X-Y structural motif required for perfect triple helix formation. The consequences include post-translational overmodification, decreased thermal stability, and delayed secretion of mutant molecules.2 The highly variable phenotype in the present kindred cannot be explained solely on the basis of the cysteine for glycine substitution but will require further exploration.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalConnective Tissue Research
Volume29
Issue number1
DOIs
StatePublished - Jan 1 1993

Keywords

  • Cysteine
  • Osteogenesis Imperfecta
  • Type I collagen

ASJC Scopus subject areas

  • Rheumatology
  • Biochemistry
  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology

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