Mutations of the Cationic Trypsinogen in Hereditary Pancreatitis

Hum Mutat. 1998;12(1):39-43. doi: 10.1002/(SICI)1098-1004(1998)12:1<39::AID-HUMU6>3.0.CO;2-P.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cations
  • DNA Primers
  • Female
  • Humans
  • Male
  • Mutation*
  • Pancreatitis / genetics*
  • Pedigree
  • Polymerase Chain Reaction
  • Trypsinogen / genetics*

Substances

  • Cations
  • DNA Primers
  • Trypsinogen