Nature Genetics
25, 213 - 216 (2000)
doi:10.1038/76088
Mutations in the gene encoding the serine protease inhibitor, Kazal type
1 are associated with chronic pancreatitisHeiko Witt1, Werner Luck1, Hans Christian Hennies2, Martin Cla en3, Andreas Kage4, Ulrich La5, Olfert Landt5
& Michael Becker11
Department of Pediatrics, Charité, Campus Virchow-Klinikum,
Humboldt University, Berlin, Germany. 2
Department of Molecular Genetics and Gene Mapping Center,
Max-Delbrück-Centrum, Berlin, Germany. 3
Department of Pediatrics, Zentralkrankenhaus 'Links
der Weser', Bremen, Germany. 4
Institute of Laboratory Medicine and Pathobiochemistry,
Charité, Campus Virchow-Klinikum, Humboldt University,
Berlin, Germany. 5
TIB MOLBIOL, Berlin, Germany
.
Correspondence should be addressed to Heiko Witt heiko.witt@charite.deChronic 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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