Next generation sequencing pitfalls in diagnosing trypsinogen (PRSS1) mutations in chronic pancreatitis
Frank Ulrich Weiß, Felix Laemmerhirt, Markus M. Lerch
Abstract
With interest we read the recent study by Hegyi et al ,1 who established that the risk for developing pancreatitis conferred by a haplotype spanning the trypsin locus (PRSS1–PRSS22 3) is strongly dependent on exogenous factors. Changes in PRSS14 or PRSS25 have long been reported to associate with either an increased or a decreased pancreatitis risk, depending on how they contribute to the activation/degradation balance within pancreatic acinar cells. Other germline changes in proteins outside the protease cascade induce pancreatic injury by interfering with intracellular protein processing6 or induction of endoplasmic reticulum stress.7 All recent guidelines agree that mutations affecting the trypsin locus confer the highest risk of developing pancreatitis and put trypsin (PRSS1) in the first line of testing in patients with suspected hereditary pancreatitis (HP).8 Challenges arising from testing these patients include not only the more than 80 known PRSS1 variants of sometimes uncertain clinical relevance (http://www.pancreasgenetics.org/), but also the progression of diagnostic technology towards next generation sequencing (NGS)—especially in conjunction with consumer genetics offered to the general …