Mutations of the cationic trypsinogen gene in patients with hereditary pancreatitis

Background: Hereditary pancreatitis has been shown to be caused by one of two mutations (R117H and N21I) of the cationic trypsinogen gene (PRSS1). Families with hereditary pancreatitis in the north of England were investigated for these mutations. The clinical features associated with each mutation were compared. Methods: In individuals from nine families with hereditary pancreatitis, DNA was screened for the R117H and N21I mutations. All five exons of the cationic trypsinogen gene were also sequenced to search for additional mutations. Haplotype analysis was carried out to identify common ancestors. Clinical data were collected. Results: The R117H mutation was identified in three families and N21I in a further five. The R117H mutation was associated with a more severe phenotype than N21I in terms of mean(s.d.) age of onset of symptoms (8.4(7.2) versus 16.5(7.1) years; P = 0.007) and requirement for surgical intervention (eight of 12 versus four of 17 patients respectively; P = 0.029). Haplotype analysis suggested that each mutation had arisen more than once. Conclusion: Two mutations in the cationic trypsinogen gene cause hereditary pancreatitis in eight of nine families originating in this region. The R117H mutation is associated with a more severe form of the disease in terms of age at onset of symptoms and requirement for surgical intervention.