Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene.

Published

Journal Article

Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg-His substitution at residue 117 of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis.

Full Text

Duke Authors

Cited Authors

  • Whitcomb, DC; Gorry, MC; Preston, RA; Furey, W; Sossenheimer, MJ; Ulrich, CD; Martin, SP; Gates, LK; Amann, ST; Toskes, PP; Liddle, R; McGrath, K; Uomo, G; Post, JC; Ehrlich, GD

Published Date

  • October 1996

Published In

Volume / Issue

  • 14 / 2

Start / End Page

  • 141 - 145

PubMed ID

  • 8841182

Pubmed Central ID

  • 8841182

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng1096-141

Language

  • eng