Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: PRSS1 MUTATIONS Part 1

PRSS1 MUTATIONS Part 1Cationic trypsinogen is among the most abundant molecules produced by pancreatic acinar cells. It plays a central role in hydrolyzing dietary proteins at lysine and arginine amino acid residues, and also in activating all other digestive proenzymes. Premature activation of trypsinogen within the pancreas leads to pancreatic autodigestion and is believed to be a key step in the pathogenesis of acute pancreatitis. Recurrent attacks of acute pancreatitis, as occur in patients with hereditary pancreatitis, eventually lead to chronic pancreatitis.

Major mutations

Mutations in codons 29 (exon 2) and 122 (exon 3) of PRSS1 cause autosomal dominant forms of hereditary pancreatitis. The codon 122 mutations usually result in an R122H substitution (older nomenclature, R117H) that eliminates a ‘fail safe’ trypsin hydrolysis site in the side chain of trypsin that connects the two halves of the molecule. The elimination of this site causes a gain-of-function mutation because prematurely activated trypsin cannot be inactivated by autolysis. The N29I mutation (older nomenclature, N21I) causes a clinical syndrome identical to the R122H mutation syndrome, although the molecular mechanism causing the gain of function is still unclear. Other less frequent mutations at codons 29 and 122 have also been identified. The common N29I and R122H mutations occur in patients from North America, Europe, Japan, and probably elsewhere. If you want to make your online shopping advantageous and safe, check out the best pharmacy to buy birth control pills without any need for a prescription, any time of the day or night with straight to the doorstep delivery.

Clinical syndrome

Approximately 80% of persons with the PRSS1 N29I or R122H mutations have recurrent episodes of acute pancreatitis during childhood. The median age of onset is roughly 10 years; chronic pancreatitis develops during the subsequent decade of the disease in about half of patients with acute pancreatitis, and pancreatic cancer occurs by age 70 years in 40% of individuals with chronic pancreatitis. Smoking more than doubles the risk of developing pancreatic cancer and reduces the median age of onset by 20 years.

This entry was posted in Pancreatic and tagged Cystic fibrosis transmembrane conductance regulator, Kazal type 1, Pancreatic secretory trypsin inhibitor, Serine protease inhibitor, Trypsin, Trypsinogen.