Human Genetics

, Volume 89, Issue 4, pp 414–418 | Cite as

A single base mutation in the gene for type III collagen (COL3A1) converts glycine 847 to glutamic acid in a family with Ehlers-Danlos syndrome type IV. An unaffected family member is mosaic for the mutation

  • A. J. Richards
  • P. N. Ward
  • P. Narcisi
  • A. C. Nicholls
  • J. C. Lloyd
  • F. M. Pope
Original Investigations
Received:
Revised:

Summary

Ehlers-Danlos syndrome type IV, an inherited connective tissue disease, is usually caused by mutations in the gene for type III collagen. Here, we describe a glycine to glutamic acid substitution in a patient with this syndrome. Previous studies had shown that fibroblasts from the patient, his mother and brother secreted a reduced amount of type III collagen and also produced an overmodified form of the protein that was preferentially retained intracellularly. Peptide mapping experiments indicated that the mutation was located within cyanogen bromide peptide 9. This was supported by chemical cleavage analysis and sequencing of cDNA encoding this region. Allele-specific oligonucleotide hybridisation of genomic DNA confirmed that a G to A mutation converted Gly 847 to Glu. The mutation was present in two other affected family members and also in a third, who was clinically unaffected. Further analysis of this unaffected individual revealed reduced mutant:normal ratios in DNA obtained from both blood and hair samples, showing that she was mosaic for the mutation.

Keywords

Glutamic Acid Connective Tissue Disease Hair Sample Cyanogen Peptide Mapping 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • A. J. Richards
    • 1
  • P. N. Ward
    • 1
  • P. Narcisi
    • 1
  • A. C. Nicholls
    • 1
  • J. C. Lloyd
    • 1
  • F. M. Pope
    • 1
  1. 1.Dermatology Research GroupClinical Research CentreHarrowUK

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