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A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering

Nature volume 356, pages 244–246 (1992)Cite this article

Abstract

IN the hereditary blistering condition epidermolysis bullosa simplex, the skin blisters on trauma following rupture of epidermal basal cells. Clinical variations range from severely incapacitating, especially in early childhood, to mild forms that may not even present clinically. Dowling–Meara epidermolysis bullosa simplex is characterized by clusters of epidermal blisters and keratin clumping in the cytoplasm1; recent reports describe potentially causal mutations in keratin 14 (refs 2, 3). Here we describe a "complementary' mutation at the other end of the other keratin expressed by these cells (K5, coexpressed with K14), a change from a Glu to a Gly in the helix termination peptide, detected by altered antibody binding and confirmed by sequencing using the polymerase chain reaction. The two conserved helix boundary peptides are predicted to be essential for filament assembly, and the requirement for two complementary (type I and type II) keratins is absolute. Epidermolysis bullosa simplex diseases demonstrate the function of the keratin cytoskeleton in resisting compaction stresses which otherwise lead to cell lysis.

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Authors and Affiliations

  1. CRC Cell Structure Research Group, Cancer Research Campaign Laboratories, Department of Anatomy and Physiology, Medical Sciences Institute, University of Dundee, Dundee, DD1 4HN, UK

    E. B. Lane & E. L. Rugg

  2. Experimental Dermatology Laboratory and ICRF Skin Tumour Laboratory, 56 Ashfield Street, London, El 2BL, UK

    H. Navsaria & I. M. Leigh

  3. Department of Dermatology, North Staffordshire Royal Infirmary, Stoke-on-Trent, ST4 7LN, UK

    A. H. M. Heagerty

  4. Department of Cell Pathology, Institute of Dermatology, UMDS, St Thomas's Hospital, London, SE1 7EH, UK

    A. Ishida-Yamamoto & R. A. J. Eady

Authors
  1. E. B. Lane
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  2. E. L. Rugg
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  3. H. Navsaria
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  4. I. M. Leigh
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  5. A. H. M. Heagerty
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  6. A. Ishida-Yamamoto
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  7. R. A. J. Eady
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Lane, E., Rugg, E., Navsaria, H. et al. A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering. Nature 356, 244–246 (1992). https://doi.org/10.1038/356244a0

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