PRSS1-Gen

Hereditary pancreatitis was first described by Comfort and Steinberg in 1952 in a study of a family with four affected generations.

PRSS1 is the acronym for "serine protease gene 1, a gene located on chromosome 7q34. The gene encodes an enzymatic protein, cationic trypsinogen, which belongs to the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved into its active form (trypsin) in the small intestine. It has an enzymatic cleaving effect on peptide bonds involving the carboxyl group of lysine or arginine.

A specific region of trypsin is bound to a calcium molecule. As long as trypsin is bound to calcium, the enzyme is protected from degradation. After digestion is complete, when trypsin is no longer needed, the calcium molecule is removed from the enzyme, allowing trypsin to be broken down.

Evidence suggests that mutations in the PRSS1 gene increase the autocatalytic conversion of trypsinogen to active trypsin, likely causing premature intrapancreatic trypsinogen activation that disrupts the intrapancreatic balance of proteases and their inhibitors. Mutations in the PRSS1 gene are associated with hereditary pancreatitis. Conversely, certain variants (p.G191R variant) in the serine protease 2 (PRSS2) gene provide protection against chronic pancreatitis (Witt H et al.20

1. Lerch MM, Gorelick FS: Early trypsinogen activation in acute pancreatitis. Gastroenterology Clinical North America 84: 549-563
2. McGaughran JM et al.(2004) Hereditary pancreatitis in a family of Aboriginal descent Journal Pediatric Child Health 40: 487-489.
3. Rinderknecht H (1986). Activation of pancreatic zymogens. Normal activation, premature intrapancreatic activation, protective mechanisms against inappropriate activation. Digestive Disease Science 31: 314-321.
4. Witt H et al.(2006) A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis. Nat Genet 38:668-673.