PRSS1

About PRSS1

PRSS1 on chromosome 7q34 encodes cationic trypsinogen, the most abundant form of the inactive precursor of trypsin secreted by the pancreas. Trypsinogen is normally activated in the small intestine, and the pancreas has several protective mechanisms against premature activation, including the inhibitor SPINK1 and trypsin self degradation. Gain of function PRSS1 variants cause hereditary pancreatitis, an autosomal dominant condition with recurrent episodes of acute pancreatitis typically starting in childhood, progressing to chronic pancreatitis with pain, calcifications, exocrine insufficiency, and diabetes, and with a substantially increased lifetime risk of pancreatic cancer. In 1996 the R122H variant was identified as the first cause of hereditary pancreatitis, making it one of the first genetic causes of a pancreatic disease. R122H removes a site at which trypsin can cleave and inactivate itself, so prematurely activated trypsin persists inside the pancreas. N29I is another common variant. SPINK1, CFTR, CTRC, and CPA1 are other genes associated with pancreatitis susceptibility, and copy number gains of PRSS1 also cause disease. Management includes pain control, pancreatic enzyme replacement for insufficiency, endoscopic or surgical treatment of ductal complications, management of diabetes, and in some patients total pancreatectomy with islet autotransplantation. Genetic testing is used to evaluate unexplained recurrent or early onset pancreatitis.