Mutational screening of the cationic trypsinogen gene in a large cohort ofsubjects with idiopathic chronic pancreatitis

Several missense mutations, including R122H, N29I, K23R, A16V and D22G, in the cationic trypsinogen gene (PRSS1), have been associated with certain fo rms of hereditary pancreatitis (HP). Their occurrence in the idiopathic chr onic pancreatitis (ICP) and whether novel mutations could be identified in PRSS1 remain to be further evaluated. These were addressed by the mutationa l screening of the entire coding sequence and the intronic/exonic boundarie s of the PRSS1 gene in 221 ICP subjects, using a previously established den aturing gradient gel electrophoresis technique. Among the known PRSS1 mutat ions, only the R122H was detected in a single subject and the A16V in two s ubjects in the cohort, strengthening that HP-associated PRSS1 mutations are rare in ICP. Additional missense mutations, including P36R, E79K, G83E, K9 2N and V123M, were identified once separately. By analogy with the known PR SS1 mutations, predisposition to pancreatitis by some of them, particularly the V123M autolysis cleavage site mutation, is suspected. Functional analy sis is expected to clarify their possible medical consequences.