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Lethal osteogenesis imperfecta: abnormal collagen metabolism and biochemical characteristics of hypophosphatasia

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Abstract

We have examined collagen from a patient with the rare type IIC form of perinatally lethal osteogenesis imperfecta, in whom biochemical characteristics of hypophosphatasia were also apparent. In addition to normal α1(I) and α2(I) chains, there were chains overmodified along their lengths. Unexpectedly, the thermal stability of molecules containing these chains was normal. This suggests the existence of a structural mutation causing delayed triple helix formation, situated in either the α1(I) or α2(I) C-terminal propeptide. Since collagen synthesised by fibroblasts from each of the patient's parents was normal, the mutation was probably newly arising and dominant. In contrast to other reported cases of lethal osteogenesis imperfecta, not only was the secretion of collagen by cultured fibroblasts considerably retarded, but that of non-collagenous proteins was also severely impaired.

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Abbreviations

OI:

osteogenesis imperfecta

EMEM:

Eagle's minimum essential medium

SDS-PAGE:

sodium dodecyl sulphate-polyacrylamide gel electrophoresis

Tm :

thermal denaturation temperature

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Author information

Authors and Affiliations

  1. Division of Metabolism, Department of Paediatrics, University of Zürich, Zürich, Switzerland

    P. M. Royce & B. Steinmann

  2. Children's Hospital Wildermeth, Biel, Switzerland

    A. Blumberg & R. P. Zurbrügg

  3. Institute for Pathological Anatomy, University of Bern, Switzerland

    A. Zimmermann

  4. Department of Clinical Chemistry, Inselspital, University of Bern, Bern, Switzerland

    J. -P. Colombo

Authors
  1. P. M. Royce
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  2. A. Blumberg
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  3. R. P. Zurbrügg
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  4. A. Zimmermann
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  5. J. -P. Colombo
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  6. B. Steinmann
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Royce, P.M., Blumberg, A., Zurbrügg, R.P. et al. Lethal osteogenesis imperfecta: abnormal collagen metabolism and biochemical characteristics of hypophosphatasia. Eur J Pediatr 147, 626–631 (1988). https://doi.org/10.1007/BF00442478

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  • DOI: https://doi.org/10.1007/BF00442478

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