Screening for human cationic trypsinogen (PRSS1) and trypsinogen inhibitor gene (SPINK1) mutations in a Finnish family with hereditary pancreatitis.
OBJECTIVE
Mutations in the cationic trypsinogen gene (PRSS1) have been linked with hereditary pancreatitis (HP). A change in R122H in the third exon is one of the mutations most frequently associated with HP. A mutation N34S in the serine protease inhibitor Kazal type 1 gene has also been shown to be linked with HP. The purpose of this study was to report on the incidence of PRSS1 and SPINK1 mutations in a Finnish family with HP and to correlate the findings to the clinical symptoms.


METHODS
The study included 36 individuals from one Finnish family with HP (21 M, 15 F, median age 38 years). All individuals underwent abdominal ultrasound and laboratory tests (glucose, faecal elastase-1 test). Blood samples were taken for mutational analysis of PRSS1 (R122H, N29I and A16V) and SPINK1 (N34S).


RESULTS
Ten (28%) individuals were affected by mutations: the most frequent mutation was R122H, affecting 8 (22%) individuals; 2 (6%) individuals were affected by the N34S mutation and none by the other tested mutations (N29I and A16V). Four out of eight (50%) R122H-positive individuals had a diagnosis of chronic pancreatitis without other known aetiologies. Four out of five (80%) male individuals with the R122H mutation also had clinical pancreatitis, whereas none of the three mutation-positive females had any signs or symptoms of chronic pancreatitis. The two individuals with the N34S mutation did not have any signs of chronic pancreatitis.


CONCLUSIONS
In the investigated Finnish pedigree with HP, the PRSS1 mutation R122H is linked with chronic disease. Although the SPINK1 mutation (N34S) was also observed in two individuals, it was not linked with the disease.
Räty
Sari
S
Departments of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland. raty.sari@kulumbus.fi
Piironen
Anneli
A
Babu
Mohan
M
Pelli
Hanna
H
Sand
Juhani
J
Uotila
Sanna
S
Nordback
Isto
I
Herzig
Karl-Heinz
KH
D000328:Adult; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005387:Finland; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010195:Pancreatitis / Q000235:genetics*; D010375:Pedigree; D014357:Trypsin; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen / Q000235:genetics*
D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin