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

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 cause d by either increased proteolytic activity or decreased protease inhibition . Several studies have demonstrated mutations in the cationic trypsinogen g ene (PRSS1) in patients with hereditary(1-3) or idiopathic(4) CP. It is tho ught that these mutations result in increased trypsin activity within the p ancreatic parenchyma. Most patients with idiopathic or hereditary CP. howev er, 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 ser ine protease inhibitor. Kazal type 1 (SPINK1). a pancreatic trypsin inhibit or. We found mutations in 23% of the patients. In 18 patients. 6 of whom we re 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.