Genetic mutations in exons 3 and 4 of the pancreatic secretory trypsin inhibitor in patients with pancreatitis

Purpose. We hypothesized that mutations in the pancreatic secretory trypsin inhibitor (PSTI) gene could promote autodigestion, leading to acute or chr onic pancreatitis. Our investigation involved mutation analysis of the PSTI gene in patients with acute or chronic pancreatitis. Methods. Mutation ana lysis for the PSTI gene was performed in patients with acute or chronic pan creatitis. Unrelated healthy volunteers and family members of a chronic pan creatitis patient with point mutations in the PSTI gene were also analyzed. Results. Two types of single-point mutation in the PSTI gene were observed in one patient with chronic pancreatitis: (34)Asn (AAT)-to-Ser (AGT) (101 A > G N34S: N34S) in exon 3, and (67)Arg (CGC)-to-Cys (TGC) (199 C > T R67C : R67C) in exon 4. No mutations with aminoacid substitution were found in o ther patients or in the volunteer group. In the patient with the PSTI gene mutations, no additional mutations were observed in the cationic trypsinoge n gene. The family study revealed that the mother and a maternal uncle were homozygotes for the N34S mutation, while the father and brother were compo und heterozygotes for the N34S and R67C mutations. The uncle (N34S/N34S) sh owed clinical manifestations of pancreatitis, but the other family members did not. Conclusions. The N34S mutation may cause a predisposition to pancr eatitis, with incomplete penetrance. However, with the limited information available, it is not known whether the R67C mutation promotes pancreatitis.