Prevalence of R117H mutation in the cationic trypsinogen gene in patients with hereditary pancreatitis

Background: The R117H mutation of the cationic trypsinogen (CT) gene (G to A mutation in exon 3), located on chromosome 7q35, is one of the known mutations that is linked to hereditary pancreatitis (HP) and is thought to alter a trypsin recognition site responsible for the breakdown of inappropriately activated trypsinogen so resulting in pancreatitis. The aim of this study was to determine the prevalence of this mutation in patients with HP and to correlate presence of the mutation with disease characteristics. Methods: Polymerase chain reaction amplification of the third exon of the CT gene was performed on blood DNA. This was digested by the restriction endonuclease Afl III and fragments were sized by agarose gel electrophoresis. Haplotype analysis was carried out using three short tandem repeat markers in the region of the CT gene. Results: Seven discrete families with HP (three to seven generations) were identified (22 affected individuals). The mutation was present in individuals from three of the seven families. It was absent in all affected individuals from the other four families. A higher proportion of patients requiring pancreatic surgery was seen in families expressing this mutation (eight of 14 versus one of eight, P = 0·016). Mean(s.d.) age of onset was similar in both groups (7·9(5·8) versus 6·3(10·1) years, P = 0·13). In the affected families, the same high-risk haplotype was present in two families, suggesting a common ancestor. The third family carried a unique haplotype. Conclusion: A single G to A mutation in the third exon of the CT gene was found in three families with HP originating from this region and appears to be associated with more severe disease. Further work is being undertaken to analyse the CT gene more fully in families in which this common first mutation was not identified. © 1999 British Journal of Surgery Society Ltd