Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Plectin deficiency results in muscular dystrophy with epidermolysis bullosa

Nature Genetics volume 13, pages 450–457 (1996)Cite this article

Abstract

We report that mutation in the gene for plectin, a cytoskeleton–membrane anchorage protein, is a cause of autosomal recessive muscular dystrophy associated with skin blistering (epidermolysis bullosa simplex). The evidence comes from absence of plectin by antibody staining in affected individuals from four families, supportive genetic analysis (localization of the human plectin gene to chromosome 8q24.13–qter and evidence for disease segregation with markers in this region) and finally the identification of a homozygous frameshift mutation detected in plectin cDNA. Absence of the large multifunctional cytoskeleton protein plectin can simultaneously account for structural failure in both muscle and skin.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Article 24 September 2020

Ajoy Bardhan, Leena Bruckner-Tuderman, … Adrian H. Heagerty

References

  1. Fine, J.-D. et al. Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa. J. Am. Acad. Derm. 24, 119–135 (1991).

    Article  CAS  PubMed  Google Scholar 

  2. Eady, R.A.J. & Dunnill, M.G.S. Epidermolysis bullosa: hereditary skin fragility diseases as paradigms in cell biology. Arch. Derm. Res. 287, 2–9 (1994).

    Article  CAS  PubMed  Google Scholar 

  3. Christiano, A.M. & Uitto, J. Molecular complexity of the cutaneous basement membrane zone. Revelations from the paradigms of epidermolysis bullosa. Exp. Derm. 5, 1–11 (1996).

    Article  CAS  PubMed  Google Scholar 

  4. Leigh, I.M. & Lane, E.B. Mutations in the genes for epidermal keratins in epidermolysis bullosa and epidermolytic hyperkeratosis. Arch. Derm. 129, 1571–1577 (1993).

    Article  CAS  PubMed  Google Scholar 

  5. Lane, E.B. Keratin diseases. Curr. Opin. Genet. Dev. 4, 412–418 (1994).

    Article  CAS  PubMed  Google Scholar 

  6. Niemi, K.M., Sommer, H., Kero, M., Kanerva, L. & Haltia, M. Epidermolysis bullosa simplex associated with muscular dystrophy with recessive inheritance. Arch. Derm. 124, 551–554 (1988).

    Article  CAS  PubMed  Google Scholar 

  7. Fine, J.-D. et al. Autosomal recessive epidermolysis bullosa simplex. Arch. Derm. 125, 931–938 (1989).

    Article  CAS  PubMed  Google Scholar 

  8. Doriguzzi, C. et al. Congenital muscular dystrophy associated with familial junctional epidermolysis bullosa lethalis. Eur. Neurol. 33, 454–460 (1993).

    Article  CAS  PubMed  Google Scholar 

  9. Wiche, G., Krepler, R., Artlieb, U., Pytela, R. & Denk, H. Occurrence and immunolocalization of plectin in tissues. J. Cell Biol. 97, 887–901 (1983).

    Article  CAS  PubMed  Google Scholar 

  10. Wiche, G., Krepler, R., Artlieb, U., Pytela, R. & Aberer, W. Identification of plectin in different human cell types and immunolocalization at epithelial basal cell surface membranes. Exp. Cell Res. 155, 43–49 (1984).

    Article  CAS  PubMed  Google Scholar 

  11. Foisner, R. et al. A panel of monoclonal antibodies to rat plectin: distinction by epitope mapping and immunoreactivity with different tissues and cell lines. Acta Histochem .(Jena) 96, 421–438 (1994).

    Article  CAS  Google Scholar 

  12. Hieda, Y., Nishizawa, Y., Uematsu, J. & Owaribe, K. Identification of a new hemidesmosomal protein, HD1: a major high molecular mass component of isolated hemidesmosomes. J. Cell Biol. 116, 1497–1506 (1992).

    Article  CAS  PubMed  Google Scholar 

  13. McLean, W.H.I. & Lane, E.B. Intermediate filaments in disease. Curr. Opin. Cell Biol. 7, 118–125 (1995).

    Article  CAS  PubMed  Google Scholar 

  14. Legan, P.K., Collins, J.E. & Garrod, D.R. The molecular biology of desmosomes and hemidesmosomes: ‘what's in a name?’. BioEssays 14, 385–392 (1992).

    Article  CAS  PubMed  Google Scholar 

  15. Kurpakus, M.A. & Jones, J.C.R. A novel hemidesmosomal plaque component: tissue distribution and incorporation into assembling hemidesmosomes in an in vivo model. Exp. Cell Res. 194, 139–146 (1991).

    Article  CAS  PubMed  Google Scholar 

  16. Tanaka, T. et al. Production of rabbit antibodies against carboxy-terminal epitopes encoded by bullous pemphigoid cDNA. J. Invest. Derm. 94, 617–623 (1990).

    Article  CAS  PubMed  Google Scholar 

  17. Wiche, G. et al. Cloning and sequencing of rat plectin indicates a 466-kD polypeptide chain with a three-domain structure based on a central alpha-helical coiled coil. J. Cell Biol. 114, 83–99 (1991).

    Article  CAS  PubMed  Google Scholar 

  18. Kelsell, D.P. et al. Development of a panel of monochromosomal somatic cell hybrids for rapid gene mapping. Ann. Hum. Genet. 59, 233–241 (1995).

    Article  CAS  PubMed  Google Scholar 

  19. Liu, C.-G., Maercker, C., Castañon, M., Hauptmann, R. & Wiche, G. Human plectin: organization of the gene, sequence analysis, and chromosome localization (8q24). Proc. Natl. Acad. Sci. USA 93, 4278–4283 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kelsell, D.P., Black, D.M., Bishop, D.T. & Spurr, N.K. Genetic analysis of the BRCA1 region in a large breast/ovarian cancer family: refinement of the minimal region containing BRCA1. Hum. Mol. Genet. 2, 1823–1828 (1993).

    Article  CAS  PubMed  Google Scholar 

  21. Cooper, D.N. Human gene mutation affecting RNA processing and translation. Ann. Med. 25, 11–17 (1993).

    Article  CAS  PubMed  Google Scholar 

  22. Cui, Y. Hagan, K.W., Zhang, S.A. & Peltz, S.W. Identification and characterization of genes that are required for the accelerated degradation of mRNAs containing a premature translational termination codon. Genes Dev. 9, 423–436 (1995).

    Article  CAS  PubMed  Google Scholar 

  23. Wiche, G., Plectin: General overview and appraisal of its potential role as a subunit protein of the cytomatrix. CRC Crit. Rev. Biochem. Mol. Biol. 24, 41–67 (1989).

    Article  CAS  Google Scholar 

  24. Wiche, G. High-Mr microtubule-associated proteins: properties and functions. Biochem. J. 259, 1–12 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jones, J.C. & Green, K.J. Intermediate filament-plasma membrane interactions. Curr. Opin. Cell Biol. 3, 127–132 (1991).

    Article  CAS  PubMed  Google Scholar 

  26. Foisner, R., Bohn, W., Mannweiler, K. & Wiche, G. Distribution and ultrastructure of plectin arrays in subclones of rat glioma C-6 cells differing in intermediate filament protein (vimentin) expression. J. Struct. Biol. 115, 304–317 (1995).

    Article  CAS  PubMed  Google Scholar 

  27. Wiche, G., Gromov, D., Donovan, A., Castanon, M.J. & Fuchs, E. Expression of plectin mutant cDNA in cultured cells indicates a role of COOH-terminal domain in intermediate filament association. J. Cell Biol. 121, 607–619 (1993).

    Article  CAS  PubMed  Google Scholar 

  28. Ishida-Yamamoto, A. et al. Epidermolysis bullosa simplex (Dowling-Meara type) is a genetic disease characterized by an abnormal keratin-filament network involving keratins K5 and K14. J. Invest. Derm. 97, 959–968 (1991).

    Article  CAS  PubMed  Google Scholar 

  29. Rugg, E.L. et al. A functional “knockout” of human keratin 14. Genes Dev. 8, 2563–2573 (1994).

    Article  CAS  PubMed  Google Scholar 

  30. McMillan, J.R. & Eady, R.A.J. Ontogeny of hemidesmosomes in human fetal digit skin. Arch. Derm. Res. 288, 91–97 (1996).

    Article  CAS  PubMed  Google Scholar 

  31. Campbell, K.P. Three muscular dystrophies: loss of cytoskeletal-extracellular matrix linkage. Cell 80, 675–679 (1995).

    Article  CAS  PubMed  Google Scholar 

  32. Guo, L. et al. Gene targeting of BPAG1: abnormalities in mechanical strength and cell migration in stratified epithelia and neurologic degeneration. Cell 81, 233–234 (1995).

    Article  CAS  PubMed  Google Scholar 

  33. Olaisen, B. & Gedde-Dahl Jr, T. GPT-epidermolysis bullosa simplex (EBS Ogna) linkage in man. Hum. Hered. 23, 189–196 (1973).

    Article  CAS  PubMed  Google Scholar 

  34. Brown, A., Bernier, G., Mathieu, M., Rossant, J. & Kothary, R. The mouse dystonia musculorum gene is a neural isoform of bullous pemphigoid antigen 1. Nature Genet. 10, 301–306 (1995).

    Article  CAS  PubMed  Google Scholar 

  35. Vaughan-Jones, S.A., Palmer, I., Bhogal, B.S., Eady, R.A.J. & Black, M.M. The use of Michel's transport medium for immunfluorescence and immunoelectron microscopy in autoimmune bullous diseases. J. Cut. Path. 22, 365–370 (1995).

    Article  Google Scholar 

  36. Kennedy, A.R. et al. Abnormal binding of an anti-amnion antibody provides a novel diagnostic probe for junctional epidermolysis bullosa. Br. J. Derm. 113, 651–659 (1985).

    Article  CAS  Google Scholar 

  37. Verrando, P. et al. Monoclonal antibody GB3 defines a widespread defect of several basement membranes and a keratinocyte dysfunction in patients with junctional epidermolysis bullosa. Lab. Invest. 64, 84–92 (1991).

    Google Scholar 

  38. Matsui, C. et al. γ2 chain of laminin 5 is recognized by monoclonal antibody GB3. J. Invest. Derm. 105, 648–652 (1995).

    Article  CAS  PubMed  Google Scholar 

  39. Sonnenberg, A., Janssen, H., Hogervorst, F., Calafat, J. & Hilgers, J. A complex of platelet glycoproteins Ic and IIa identified by a rat monoclonal antibody. J. Biol. Chem. 262, 10376–10383 (1987).

    CAS  PubMed  Google Scholar 

  40. Kennel, S.J. et al. Second generation monoclonal antibodies to the human integrin alpha 6 and beta 4. Hybridoma 9, 243–255 (1990).

    Article  CAS  PubMed  Google Scholar 

  41. Fine, J.-D., Horiguchi, Y. & Couchman, J.R. 19-DEJ-1, a hemidesmosome-anchoring filament complex associated monoclonal antibody. Arch. Derm. 125, 520–523 (1989).

    Article  CAS  PubMed  Google Scholar 

  42. Bancroft, J.D. & Stevens, A. Theory and practice of histological techniques (Churchill Livingstone, London, 1996).

  43. Richardson, K.C., Jarret, L. & Finke, E.H. Embedding in epoxy resins for ultrathin sectioning in electron microscopy. Stain Technol. 35, 313–323 (1960).

    Article  CAS  PubMed  Google Scholar 

  44. Eady, R.A.J. in Methods in Skin Research (eds Skerrow, D. & Skerrow, C. J.) 1-36 (John Wiley& Sons, Chichester, 1985).

    Google Scholar 

  45. Shimizu, H., McDonald, J.N., Kennedy, A.R. & Eady, R.A.J. Demonstration of intra- and extracellular localization of bullous pemphigoid antigen using cryofixation and freeze substitution for post-embedding immunoelectron microscopy. Arch. Derm. Res. 281, 443–448 (1989).

    Article  CAS  PubMed  Google Scholar 

  46. Pearson, W.R. & Lipman, J.D. Improved tools for biological sequence comparison. Proc. Natl. Acad. Sci. USA 85, 2444–2448 (1988).

    Article  CAS  Google Scholar 

  47. Parrish, J.E., Wang, Y., Wagner, M.J. & Wells, D.E. Alignment of physical and genetic maps of human 8q23–qter using a somatic cell hybrid mapping panel. Somat. Cell Genet. 20, 143–146 (1994).

    Article  CAS  Google Scholar 

  48. Cottingham, R.W., Idury, R.M. & Schaffer, A.A. Faster sequential genetic linkage computations. Am. J. Hum. Genet. 53, 252–263 (1993).

    PubMed  PubMed Central  Google Scholar 

  49. Gache, Y. et al. J. Clin. Invest. 97, 2289–2298 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. McLean, W.H.I. et al. Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization. Genes Dev. (in the press).

Download references

Author information

Authors and Affiliations

  1. CRC Cell Structure Res Group, Cancer Res Campaign Laboratories, Dept of Anatomy & Physiology, Medical Sciences Inst, Univ of Dundee, Dundee, DDl 4HN, UK

    F.J.D. Smith, E.L. Rugg, W.H.I. McLean & E.B. Lane

  2. St. John's Inst of Dermatol, United Medical and Dental Schools, St Thomas's Hospital, London, SE1 7EH, UK

    R.A.J. Eady & J.R. McMillan

  3. Academic Dept of Dermatol (IML)& Dept of Morbid Anatomy (JFG), St Bartholomew's & Royal London School of Medicine & Dentistry, Queen Mary & Westfield Coll, London, E1 2BL, UK

    I.M. Leigh & J.F. Geddes

  4. ICRF Clare Hall Laboratories, Blanche Lane, South Mimms, Potter's Bar, Hertfordshire, EN6 3LD, UK

    D.P. Kelsell, S.P. Bryant & N.K. Spurr

  5. Dermatol Clinic, Univ of Marburg, Deutschhausstraβe 9, D-35037, Marburg, Germany

    G. Kirtschig

  6. Pediatric Clinic, Molecular Biol Laboratory, Citta Univ, VialeA Doria 6, 95100, Catania, Italy

    G. Milana

  7. St. Luke's Hospital, Guardamangia, Malta

    A.G. de Bono

  8. Biological Systems, Graduate School of Human Informatics, Nagoya Univ, Nagoya, 464-01, Japan

    K. Owaribe

  9. Inst of Biochemistry and Molecular Cell Biol, Vienna Biocenter, Dr. Bohrgasse9, A-1030, Vienna, Austria

    G. Wiche

  10. Dept of Dermatol and Cutaneous Biol, Jefferson Medical Coll, Thomas Jefferson Univ, Philadelphia, Pennsylvania, USA

    L. Pulkkinen & J. Uitto

  11. Division of Medical Genetics, Kuopio Univ Hospital, 70210, Kuopio, Finland

    L. Pulkkinen

Authors
  1. F.J.D. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R.A.J. Eady
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I.M. Leigh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J.R. McMillan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E.L. Rugg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D.P. Kelsell
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S.P. Bryant
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. N.K. Spurr
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J.F. Geddes
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G. Kirtschig
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. G. Milana
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A.G. de Bono
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. K. Owaribe
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. G. Wiche
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. L. Pulkkinen
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. J. Uitto
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. W.H.I. McLean
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. E.B. Lane
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, F., Eady, R., Leigh, I. et al. Plectin deficiency results in muscular dystrophy with epidermolysis bullosa. Nat Genet 13, 450–457 (1996). https://doi.org/10.1038/ng0896-450

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0896-450

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing