A father and daughter both developed recurrent acute pancreatitis beginning in childhood. The daughter now has chronic calcific pancreatitis at age 28. Genetic testing reveals a gain-of-function mutation transmitted in an autosomal dominant pattern. Which gene is involved, and what additional malignancy risk does it confer?

• A SPINK1, with markedly raised risk of melanoma
• B PRSS1, with markedly raised lifetime risk of pancreatic ductal adenocarcinoma ✓
• C CFTR, with markedly raised risk of cholangiocarcinoma
• D CTRC, with markedly raised risk of pancreatic neuroendocrine tumor

Explanation

Hereditary pancreatitis results from autosomal dominant gain-of-function mutations in PRSS1, encoding cationic trypsinogen, which prematurely activates trypsin inside the pancreas and initiates autodigestion. Recurrent attacks progress to chronic calcific pancreatitis, and cumulative lifetime risk of pancreatic ductal adenocarcinoma is greatly elevated, approaching 40 percent in some families. SPINK1 and CFTR act as modifiers or recessive susceptibility genes and do not carry this inheritance pattern or cancer risk.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.