Autosomal dominant pancreatitis with increased cancer risk in the studied Thai family is most likely due to missense (R116C) mutation in the PRSS1 gene.
The R122H transgenic mouse failed to develop a spontaneous pancreatitis but a repeatedly provoked cerulein-induced pancreatitis led to a slightly more severe pancreatitis.
Two subjects from HP families (including a 93 year old subject with PRSS1 R122H without pancreatitis), one with chronic pancreatitis and one with a normal pancreas, were studied.
The R122H transgenic mouse failed to develop a spontaneous pancreatitis but a repeatedly provoked cerulein-induced pancreatitis led to a slightly more severe pancreatitis.
Two subjects from HP families (including a 93 year old subject with PRSS1 R122H without pancreatitis), one with chronic pancreatitis and one with a normal pancreas, were studied.
Five mutations (R122H, N29I, A16V, D22G and K23R) in cationic trypsinogen and two mutations (N34S and M1T) in the PSTI/SPINK1 gene have been found to correlate significantly with the onset of pancreatitis.
Five mutations (R122H, N29I, A16V, D22G and K23R) in cationic trypsinogen and two mutations (N34S and M1T) in the PSTI/SPINK1 gene have been found to correlate significantly with the onset of pancreatitis.
Five mutations (R122H, N29I, A16V, D22G and K23R) in cationic trypsinogen and two mutations (N34S and M1T) in the PSTI/SPINK1 gene have been found to correlate significantly with the onset of pancreatitis.
Five mutations (R122H, N29I, A16V, D22G and K23R) in cationic trypsinogen and two mutations (N34S and M1T) in the PSTI/SPINK1 gene have been found to correlate significantly with the onset of pancreatitis.
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.
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.
These individuals and 50 patients with pHPT without pancreatitis were analyzed for mutations in the serine protease inhibitor Kazal type I (SPINK1) gene (N34S) and the cationic trypsinogen gene (PRSS1) (N29I, R122H) by melting curve analysis and DNA sequencing.
These individuals and 50 patients with pHPT without pancreatitis were analyzed for mutations in the serine protease inhibitor Kazal type I (SPINK1) gene (N34S) and the cationic trypsinogen gene (PRSS1) (N29I, R122H) by melting curve analysis and DNA sequencing.
Four of 25 patients with pHPT and pancreatitis carried the N34S missense mutation in the SPINK1 gene (16%), while all 50 controls (pHPT without pancreatitis) showed no mutation in SPINK1 or PRSS1 genes (P < 0.05 vs controls, P < 0.001 vs general population).
These individuals and 50 patients with pHPT without pancreatitis were analyzed for mutations in the serine protease inhibitor Kazal type I (SPINK1) gene (N34S) and the cationic trypsinogen gene (PRSS1) (N29I, R122H) by melting curve analysis and DNA sequencing.
This problematic trend is notably illustrated by two recent studies that classified the p.A121T PRSS1 variant as pancreatitis associated, in large part owing to its intimate proximity to arginine-122, the residue affected by the disease causing p.R122H mutation.
This problematic trend is notably illustrated by two recent studies that classified the p.A121T PRSS1 variant as pancreatitis associated, in large part owing to its intimate proximity to arginine-122, the residue affected by the disease causing p.R122H mutation.
This problematic trend is notably illustrated by two recent studies that classified the p.A121T PRSS1 variant as pancreatitis associated, in large part owing to its intimate proximity to arginine-122, the residue affected by the disease causing p.R122H mutation.
The SPINK-1/N34S mutation predisposes to early onset IP and more frequent acute flares of pancreatitis that might ultimately lead to pancreatic insufficiency.
While rs62228256 was not validated as a risk factor (<i>P</i>=0.77), both rs13228878 (<i>P</i>=0.03) and rs10273639 (<i>P</i>=0.04) were. rs13228878 and rs10273639 are in high linkage disequilibrium (r<sup>2</sup>=0.94) and associated with elevated expression of the <i>PRSS1</i> gene, which encodes for trypsinogen, and are known risk variants for alcohol-associated and sporadic pancreatitis in adults.