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Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome

Abstract

We describe here eleven different mutations in SPINK5, encoding the serine protease inhibitor LEKTI, in 13 families with Netherton syndrome (NS, MIM256500). Most of these mutations predict premature termination codons. These results disclose a critical role of SPINK5 in epidermal barrier function and immunity, and suggest a new pathway for high serum IgE levels and atopic manifestations.

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Figure 1: Northern-blot analysis and SPINK5 representative homozygous mutations in NS families.

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References

  1. Traupe, H. The Ichthyosis. A Guide To Clinical Diagnosis, Genetic Counselling, And Therapy (Springer, Berlin, 1989).

    Google Scholar 

  2. Chavanas, S. et al. Am. J. Hum. Genet. 66, 914– 921 (2000).

    Article  CAS  Google Scholar 

  3. Magert, H.J. et al. J. Biol. Chem. 274, 21499– 21502 (1999).

    Article  CAS  Google Scholar 

  4. Werb, Z. Cell 91, 439–442 ( 1997).

    Article  CAS  Google Scholar 

  5. Lentsch, A. et al. Am. J. Pathol. 154, 239– 247 (1999).

    Article  CAS  Google Scholar 

  6. Rossi, A., Elia, G. & Santoro, M.G. J. Biol. Chem. 273, 16446– 16452 (1998).

    Article  CAS  Google Scholar 

  7. Culbertson, M.R. Trends Genet. 15, 74–80 (1999).

    Article  CAS  Google Scholar 

  8. Toomes, C. et al. Nature Genet. 23, 421– 424 (1999).

    Article  CAS  Google Scholar 

  9. Fartasch, M., Williams, M.L. & Elias, P.M. Arch. Dermatol. 135, 823– 832 (1999).

    Article  CAS  Google Scholar 

  10. Oettgen, H.C. & Geha, R.S. J. Clin. Invest. 104, 829–835 (1999).

    Article  CAS  Google Scholar 

  11. Ober, C. et al. Am. J. Hum. Genet. 66, 517– 526 (2000).

    Article  CAS  Google Scholar 

  12. Hershey, G.K., Friedrich, M.F., Esswein, L.A., Thomes, M.L. & Chatila, T.A. N. Engl. J. Med. 337 , 1720–1725 (1997).

    Article  CAS  Google Scholar 

  13. Heinzmann, A. et al. Hum. Mol. Genet. 9, 549– 559 (2000).

    Article  CAS  Google Scholar 

  14. Villa, A. et al. Cell 93, 885–896 (1998).

    Article  CAS  Google Scholar 

  15. Grand, R.J.A., Turnell, A.S. & Grabham, P.W. Biochem. J. 313, 353– 368 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the patients and their families, and S.H. Compton for critical reading of the manuscript. S.C. held a British Skin Foundation Fellowship and is a Marie Curie European Fellow. A.H. held a DEBRA Fellowship and is a Wellcome Trust Senior Fellow.

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Correspondence to Alain Hovnanian.

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Chavanas, S., Bodemer, C., Rochat, A. et al. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet 25, 141–142 (2000). https://doi.org/10.1038/75977

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