Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis (original) (raw)

Nature Genetics volume 25, pages 213–216 (2000)Cite this article

Abstract

Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. In approximately one-third of all cases, no aetiological factor can be found, and these patients are classified as having idiopathic disease. Pathophysiologically, autodigestion and inflammation may be caused by either increased proteolytic activity or decreased protease inhibition. Several studies have demonstrated mutations in the cationic trypsinogen gene (PRSS1) in patients with hereditary1,2,3 or idiopathic4 CP. It is thought that these mutations result in increased trypsin activity within the pancreatic parenchyma. Most patients with idiopathic or hereditary CP, however, do not have mutations in PRSS1 (ref. 4). Here we analysed 96 unrelated children and adolescents with CP for mutations in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), a pancreatic trypsin inhibitor. We found mutations in 23% of the patients. In 18 patients, 6 of whom were homozygous, we detected a missense mutation of codon 34 (N34S). We also found four other sequence variants. Our results indicate that mutations in SPINK1 are associated with chronic pancreatitis.

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Acknowledgements

We thank the families for participation; the members of the Gesellschaft für Pädiatrische Gastroenterologie und Ernährung for providing clinical data and blood samples; C. Güldner and I. Liebner for technical assistance; and F. Rüschendorf for support in computer science.

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Authors and Affiliations

  1. Department of Pediatrics, Charité, Campus Virchow-Klinikum, Humboldt University, Berlin, Germany
    Heiko Witt, Werner Luck & Michael Becker
  2. Department of Molecular Genetics and Gene Mapping Center, Max-Delbrück-Centrum, Berlin, Germany
    Hans Christian Hennies
  3. Department of Pediatrics, Zentralkrankenhaus ‘Links der Weser’, Bremen, Germany
    Martin Claßen
  4. Institute of Laboratory Medicine and Pathobiochemistry, Charité, Campus Virchow-Klinikum, Humboldt University, Berlin, Germany
    Andreas Kage
  5. TIB MOLBIOL, Berlin, Germany
    Ulrich Laß & Olfert Landt

Authors

  1. Heiko Witt
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  2. Werner Luck
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  3. Hans Christian Hennies
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  4. Martin Claßen
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  5. Andreas Kage
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  6. Ulrich Laß
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  7. Olfert Landt
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  8. Michael Becker
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Correspondence toHeiko Witt.

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Witt, H., Luck, W., Hennies, H. et al. Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis.Nat Genet 25, 213–216 (2000). https://doi.org/10.1038/76088

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