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 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.
Teich
N
N
Medizinische Klinik und Poliklinik II, Universität Leipzig, Germany.
Mössner
J
J
Keim
V
V
D001483:Base Sequence; D002412:Cations; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010195:Pancreatitis / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D014362:Trypsinogen / Q000235:genetics*
D002412:Cations; D017931:DNA Primers; D014362:Trypsinogen