Mutations of the cationic trypsinogen in hereditary pancreatitis

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Abstract
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 families 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 substitution of Asn by Ile in the sixth amino acid of the active trypsin. In exons 4 and 5, silent mutations were found. In the other expressed trypsinogens, several homozygous alterations not associated to hereditary pancreatitis were identified. As a model of pathogenesis, we hypothesize that mutation of trypsinogen in exon 2 could lead to premature cleavage of the activation peptide of trypsinogen or to altered intracellular transport. Hum Mutat 12:39–43, 1998.