PRSS1 Inheritance Pattern
PRSS1 mutations follow an autosomal dominant inheritance pattern with incomplete penetrance of approximately 80%. 1, 2
Genetic Mechanism
PRSS1 (cationic trypsinogen gene) mutations are inherited in an autosomal dominant manner, meaning only one mutated copy of the gene is sufficient to cause hereditary pancreatitis 1, 3
The penetrance is incomplete at approximately 80%, which means not all individuals who inherit the mutation will develop clinical disease 2
This is not a recessive condition—individuals with just one mutated allele can develop hereditary pancreatitis 1
Clinical Implications of Dominant Inheritance
Affected individuals have a 50% chance of passing the mutation to each offspring, consistent with autosomal dominant transmission 1
The disease typically presents in childhood, often before age 10, with recurrent acute pancreatitis episodes progressing to chronic pancreatitis 2
Carriers face approximately 40% lifetime risk of pancreatic cancer, with cumulative risks of 10% at age 50,18.7% at age 60, and 53.5% at age 75 1, 2
Common Disease-Causing Mutations
The most frequent PRSS1 mutations are R122H and N29I, which account for approximately 90% of mutation-positive hereditary pancreatitis cases 1, 4
Additional rare mutations include R122C, N29T, and A16V, all following the same autosomal dominant pattern 3, 2
The R122H mutation specifically disrupts the trypsin autolysis site, preventing normal trypsin deactivation and leading to pancreatic autodigestion 1
Surveillance Considerations
PRSS1 mutation carriers with longstanding chronic pancreatitis require pancreatic cancer surveillance starting at age 40 or 20 years after the first pancreatitis attack, whichever comes first 5, 6
Screening is particularly critical given the substantially elevated cancer risk compared to the general population 5