In four
patients with
chronic pancreatitis from two hereditary
pancreatitis (HP)
families and 63 normal controls, five
exons of cationic
trypsinogen gene (PRSS1) were amplified by
PCR and it's products were analyzed by sequencing, related clinical data were also collected. All the four
patients were found
mutations in the PRSS1
gene but their clinical feature is absolutely different. Six
patients with
diabetes mellitus were found in
pedigree No. 1, it's members show
pancreatitis symptom later, at about 29, the
tumor markers (CA19-9, CA72-4) is obviously higher than the
patients in
pedigree No. 2, two
patients with
chronic pancreatitis in
pedigree No. 2, show symptom earlier without
diabetes mellitus, their clinical characterization are different too. The number of CD4+
T cell/CD8+T is very low in Ⅲ 8, but Ⅲ 7 is normal, and the level of anti-HBs of Ⅲ 8 is variable in the
course of
pancreatitis, but the phenomenon was not found in Ⅲ 7. In their PRSS1
gene two
guanosine (G) to
adenosine (A)
mutations were found in PRSS1
exon 3 of
pedigree No. 1, one was detected at 336 basyl, the other
mutation occurs at 361 basyl. The results of the
mutations were Lys →Lys and Ala →Thr. While
thymine (T) to
adenosine (A) and (
guanosine) G→(
adenosine) A
mutation in PRSS1
exon 3 was detected in the other
patient of
pedigree No. 2 (Ⅲ 8). One was 361 basyl, the other at 415 basyl. While c.415 T→A was not found in the proband of
pedigree No. 2 PRSS1
gene (Ⅲ 7). All of the
mutations were heterozygous
mutation, that is to say all of the
trypsinogen were wild type and mutant type concomitance, the normal and abnormal pathway of active
trypsinogen exist partially. At the same
time, the
mutations of
SPINK1 were not observed. Compared with the
documents and registration of NCBI, it can be concluded that PRSS1
gene had many kinds of
mutations in hereditary
pancreatitis, the heterozygous
mutations (c.336 G→A, c.415 T→A) were the novel
mutations and related with clinical
phenotype. What's more, it's the first
time that the multisite heterozygous
mutations of PRSS1
gene were reported. The presence of the
mutations in four
patients with
chronic pancreatitis, it's absence in their
relatives and the strong evolutionary conservation of the
mutation, all indicate that the
trypsinogen mutation is associated with hereditary
pancreatitis and for the first
time raises the question whether a gain or a loss of
trypsin function participates in the onset of
Chinese pancreatitis.