Mutations in exons 2 and 3 of the cationic trypsinogen gene in Japanese families with hereditary pancreatitis

Background/Aims-Single-point mutations in the cationic trypsinogen gene hav e been reported in hereditary pancreatitis kindreds in the white population . The aim of the present study was to investigate whether similar gene muta tions are present in Japanese hereditary pancreatitis kindreds. Methods-All five exons of the cationic trypsinogen gene were amplified by p olymerase chain reaction and sequenced in six Japanese families with heredi tary pancreatitis. Results-Two types of single-point mutation in the cationic trypsinogen gene , which were identical with those reported in white families with hereditar y pancreatitis, were observed in separate Japanese families with hereditary pancreatitis: (21)Asn (AAC) to lie (ATC) (N21I) in exon 2 and (117)Arg (CG C) to His (CAC) (R117H) in exon 3. Pancreatitis occurred at more advanced a ges in patients with the N21I mutation than in those with the R117H mutatio n. Besides normal polymorphisms in exons 4 and 5, no mutation was found in patients in the remaining four families with hereditary pancreatitis, 21 pa tients with sporadic chronic pancreatitis, or five normal subjects. Conclusions-These results show heterogeneity, but no racial specificity, in the cationic trypsinogen gene mutations in hereditary pancreatitis kindred s. A distinctive clinical feature for each of the mutation types is suggest ed: adult onset for the N21I mutation and childhood onset for the R117H mut ation.