SPINK1 mutations and phenotypic expression in patients with pancreatitis associated with trypsinogen mutations

Hereditary pancreatitis (HP) is an inborn disorder which leads to recurrent episodes of pancreatitis in children and young adults and is associated with exocrine pancreatic insufficiency and secondary diabetes.1–3 Several germline mutations in the cationic trypsinogen ( PRSS1 ) gene have been found to be associated with the disease phenotype, the most common of which are the R122H, N29I, and A16V mutations.4–6 The clinical significance of various other PRSS1 mutations that have been reported from isolated patients or single families is as yet unclear.7,8 In many families with HP some relatives who carry the mutation relevant to the disease will never develop pancreatitis. The prevalence of these healthy carriers varies from between 20% and 30% in families with the common R122H and N29I mutations,2,5 and may rise to nearly 80% in families with the A16V mutation.6,9 The underlying cause for this variable penetrance remains unknown, but environmental as well as genetic factors might be involved. ### Key points

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