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:

Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the γ2 subunit of nicein/kalinin (LAMININ–5)

Nature Genetics volume 6, pages 299–304 (1994)Cite this article

Abstract

We have linked Herlitz's junctional epidermolysis bullosa (H–JEB) to the gene (LAMC2) encoding the γ2 subunit of nicein/kalinin, an isolaminin (laminin–5) expressed by basal keratinocytes. In four H–JEB kindreds, a maximum two–point lod score of 5.33 at θ=0 was observed between a microsatellite near LAMC2 at 1 q25–31 and the disease. In one family, a homozygous point mutation leading to a premature stop codon (CGA to TGA) was identified in exon 3 of the gene. The segregation of the mutated allele implicates the mutation in the pathology of the disorder and corroborates the linkage results.

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. Dermatol. 24, 119–135 (1991).

    Article  CAS  Google Scholar 

  2. Epstein, E.H. Molecular genetics of epidermolysis bullosa. Science 256, 799–804 (1992).

    Article  CAS  Google Scholar 

  3. Fine, J.D. Epidermolysis bullosa: clinical aspects, pathology and recent advances in research. Int. J. Dermatol. 25, 143–157 (1986).

    Article  CAS  Google Scholar 

  4. Verrando, P. et al. Monoclonal antibody GB3, a new probe for the study of human basement membranes and hemidesmosomes. Exp. cell Res. 170, 116–128 (1987).

    Article  CAS  Google Scholar 

  5. Kallunki, P. et al. A truncated laminin chain homologous to the B2 chain: structure, spatial expression and chromosomal assignement. J. cell Biol. 119, 679–693 (1992).

    Article  CAS  Google Scholar 

  6. Vailly, J. et al. The 100-kDa chain of nicein/kalinin is a laminin B2 chain variant. Eur. J. Blochem. 219, 209–218 (1994).

    Article  CAS  Google Scholar 

  7. Gerecke, D., Wagman, D.W., Champliaud, M.F. & Burgeson, R.E. The complete primary structure for a novel lamin chain, the laminin B1 k chain. J. biol. Chem. (in the press).

  8. Baudoin, C. et al. The 150 kD subunit of the basement membrane component BM600/nicein shares homologies with the chain A of human laminin. J. invest. Dermatol. (in the press).

  9. Engel, J. Laminins and other strange proteins. Biochemistry 31, 10643–10651 (1992).

    Article  CAS  Google Scholar 

  10. Burgeson, R.E. et al. A new nomenclature for laminins. Matrix Biol. (in the press).

  11. Baudoin, C. et al. Herlitz junctional epidermolysis bullosa keratinocytes display heterogeneous defects of nicein gene expression. J. clin. Invest. (in the press).

  12. Vailly, J., et al. The genes for nicein/kalinin 125kDa and 100kDa subunits, candidates for junctional epidermolysis bullosa, map to chromosome 1q32 and 1 q25–q31. Genomics (in the press).

  13. Aberdam, D. et al. Assignement of mouse nicein (laminin 5) genes to chromosome 1 and 18. Mamm. Genome (in the press).

  14. Rousselle, P., Lunstrum, G.P., Keene, D.R. & Burgeson, R.E. Kalinin: an epithelium-specific basement membrane adhesion molecule that is a component of anchoring filaments. J. cell Biol. 114, 567–576 (1991).

    Article  CAS  Google Scholar 

  15. Carter, W.G., Ryan, M.C. & Gahr, P.J. Epilligrin, a new cell adhesion ligand for integrin α3β1 in epithelial basement membranes. Cell. 65, 599–610 (1991).

    Article  CAS  Google Scholar 

  16. Sakai, L.I., Keene, D.R., Morris, N.P. & Burgeson, R.E. Type VII collagen is a major structural component of anchoring fibrils. J. cell Biol. 114, 1567–1586 (1986).

    Google Scholar 

  17. Burgeson, R.E. Type VII collagen, anchoring fibrils and epidermolysis bullosa. J. invest. Dermatol. 101, 252–255 (1993).

    Article  CAS  Google Scholar 

  18. Verrando, P. et al. Monoclonal antibody GB3 defines a widespread defect of several basement membranes and a keratinocyte dysfunction in patient with lethal junctional epidermolysis bullosa. Lab. Invest. 64, 85–92 (1991).

    CAS  PubMed  Google Scholar 

  19. Meneguzzi, G., Marinkovich, M.P., Aberdam, D., Burgeson, R. & Ortonne, J.P. Abnormal expression of kalinin in the Herlitz's JEB epithelial basement membrane. Exp. Dermatol. 1, 221–229 (1992).

    Article  CAS  Google Scholar 

  20. Fine, J.D. 19-DEJ-1, a monoclonal antibody to the hemidesmosome-anchoring filament complex, is the only reliable immunohistochemical probe for all major forms of junctional epidermolysis bullosa. Arch. Dermatol. 126, 1187–1190 (1990).

    Article  CAS  Google Scholar 

  21. Welssenbach, J. et al. A second-generation linkage map of the human genome. Nature 359, 794–801 (1992).

    Article  Google Scholar 

  22. Group, N.C.C.M. A comprehensive genetic linkage map of the human genome. Science 258, 148–162 (1992).

    Article  Google Scholar 

  23. Bare, J.W., Lebo, R.V. & Epstein, E.H. Jr. Loss of heterozygosity at chromosome 1q22 in basal cell carcinomas and exclusion of the basal cell nevus syndrome gene from this site. Cancer Res. 52, 1494–1498 (1992).

    CAS  PubMed  Google Scholar 

  24. Verrando, P. et al. Differential immunoreactivity of antibodies to the basement membrane protein nicein (BM600) in Junctional Epidermolysis Bullosa. J. invest. Dermatol. 101, 738–743 (1993).

    Article  CAS  Google Scholar 

  25. Woodley, D.T. & McNutt, S. In Epidermolysis bullosa. Basic and clinical aspects. (eds Lin, A.N. & Carter, D.M.) 19–36 (Springer-Verlag, New York, 1992).

    Book  Google Scholar 

  26. Pulkkinen, L. et al. Mutations in the γ2 chain gene (LAMC2) of kalinin/laminin-5 in the junctional forms of epidermolysis bullosa. Nature Genet. 6, 293–298 (1994).

    Article  CAS  Google Scholar 

  27. Marinkovich, M.P., Lunstrum, G.P., Keene, D.R. & Burgeson, R.E. The dermal-epidermal junction of human skin contains a novel laminin variant. J. cell Biol. 119, 695–703 (1992).

    Article  CAS  Google Scholar 

  28. Christiano, A. M. et al. A missense mutation in type VII collagen in two affected siblings with recessive dystrophic epidermolysis bullosa. Nature Genet. 4, 62–66 (1993).

    Article  CAS  Google Scholar 

  29. Uitto, J. & Christiano, A. M. Dystrophic forms of epidermolysis bullosa. Sem. Dermatol. 12, 191–201 (1993).

    CAS  Google Scholar 

  30. Sambrook, J., Fritsch, E.F. & Maniatis, T. Molecular cloning: A laboratory manual. (Cold Spring Harbor Laboratory Press, New York, 1989).

    Google Scholar 

  31. Ortonne, J.P. et al. The epidermal antigen recognized by monoclonal antibody GB36 is very late antigen 6 (VLA-6). J. invest. Dermatol. 94, 400A (1990).

    Google Scholar 

  32. Browne, D.L. & Litt, M. Characterization of (CA)n microsatellites with degenerate sequencing primers. Nucl. Acids Res. 200, 141 (1992).

    Article  Google Scholar 

  33. Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Strategies for multilocus linkage analysis in humans. Proc. natn. Acad. Sci. U.S.A. 81, 3443–3446 (1984).

    Article  CAS  Google Scholar 

  34. Rheinwald, J.G. & Green, H. Serial cultivation of strains of human epidermal keratinocytes; the formation of keratinocyte colonies from single cells. Cell 6, 331–344 (1975).

    Article  CAS  Google Scholar 

  35. Simon, M. & Green, H. Enzymatic cross-linking of involucrin and other proteins by keratinocytes particulates in vitro. Cell 40, 677–683 (1985).

    Article  CAS  Google Scholar 

  36. Chomzynski, P. & Sacchi, N. Single step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162, 156–159 (1987).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM U385, Faculté de Médecine, 06107, Nice, cedex 2, France

    Daniel Aberdam, Marie-Florence Galliano, Joëlle Vailly, Jean-Paul Ortonne & Guerrino Meneguzzi

  2. Department of Dermatology, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107, USA

    Leena Pulkkinen, Angela M. Christiano & Jouni Uitto

  3. Department of Dermatology, University of California, San Francisco General Hospital, San Francisco, California, 94110, USA

    Jeannette Bonifas & Ervin H. Epstein Jr

  4. Biocenter and Department of Biochemistry, University of Oulu, 90570, Oulu, Finland

    Karl Tryggvason

  5. on leave of absence from Department of Obstetrics & Gynecology, Section of Prenatal Diagnosis, Kuopio University Hospital, Kuopio, Finland

    Leena Pulkkinen

Authors
  1. Daniel Aberdam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marie-Florence Galliano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joëlle Vailly
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Leena Pulkkinen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jeannette Bonifas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Angela M. Christiano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Karl Tryggvason
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jouni Uitto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ervin H. Epstein Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jean-Paul Ortonne
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Guerrino Meneguzzi
    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

Aberdam, D., Galliano, MF., Vailly, J. et al. Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the γ2 subunit of nicein/kalinin (LAMININ–5). Nat Genet 6, 299–304 (1994). https://doi.org/10.1038/ng0394-299

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0394-299

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