MUTATIONS OF THE CATIONIC TRYPSINOGEN IN HEREDITARY PANCREATITIS

Hereditary pancreatitis (OMIM 167800) is thought to be associated with a mutation of the exon 3 of cationic trypsinogen (Nature Genet (1996) : 14:141-145). This paper reports sequence data of two independent fam ilies suffering from this disease. PCR amplificates from leukocyte or buccal swab DNA showed no mutation of exon 3 of cationic trypsinogen. Instead, in exon 2, an A-to-T tranversion was found that led to the su bstitution of Asn by Tie in the sixth amino acid of the active trypsin . In exons 4 and 5, silent mutations were found. In the other expresse d trypsinogens, several homozygous alterations not associated to hered itary pancreatitis were identified. As a model of pathogenesis, we hyp othesize that mutation of trypsinogen in exon 2 could lead to prematur e cleavage of the activation peptide of trypsinogen or to altered intr acellular transport. (C) 1998 Wiley-Liss, Inc.