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SSCP detection of a Gly565Val substitution in the proα(I) collagen chain resulting in osteogenesis imperfecta type II

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Abstract

A patient with perinatal lethal osteogenesis imperfecta (OI) type II has been studied in order to identify the causative mutation. By analysis of the type I collagen produced by cultured fibroblasts from the patient, the defect was mapped to α1 cyanogen bromide peptide 7, a region corresponding to 271 amino acid residues of either the α1(I) or α2(I) collagen chains. Polymerase chain reaction (PCR) amplification of the corresponding region of the α1(I) mRNA followed by single-strand conformation polymorphism analysis of restriction enzyme digestions of the PCR products allowed further mapping of the mutation to a small region of COL1A1. A heterozygous transversion of G to T within the last glycine codon of exon 32 was identified by DNA sequence analysis. This resulted in the substitution of glycine-565 by a valine residue, disrupting the repeating Gly-Xaa-Yaa sequence that is obligatory for correct formation of the collagen molecule. The mutation was shown to have occurred de novo and is thought to result in the OI phenotype.

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Author notes

  1. Allan M. Lund

    Present address: Division of Clinical Genetics, Department of Paediatrics, University of Copenhagen, DK-2000, Copenhagen, Denmark

Authors and Affiliations

  1. Department of Genetics, University of Leicester, LE1 7RH, Leicester, UK

    Katrina Mackay & Raymond Dalgleish

  2. Division of Metabolism, Department of Paediatrics, University of Zurich, CH-8032, Zurich, Switzerland

    Allan M. Lund, Michael Raghunath & Beat Steinmann

Authors
  1. Katrina Mackay
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  2. Allan M. Lund
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  3. Michael Raghunath
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  4. Beat Steinmann
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  5. Raymond Dalgleish
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Mackay, K., Lund, A.M., Raghunath, M. et al. SSCP detection of a Gly565Val substitution in the proα(I) collagen chain resulting in osteogenesis imperfecta type II. Hum Genet 91, 439–444 (1993). https://doi.org/10.1007/BF00217768

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  • DOI: https://doi.org/10.1007/BF00217768

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