Identification of a novel frame-shift mutation in PRSS1 gene in Han patients with autoimmune pancreatitis.

OBJECTIVE To detect mutations of trypsinogen gene (PRSS1) in patients with autoimmune pancreatitis (AIP) and to determine the underlying pathogenesis. METHODS DNA sequencing was used to detect full-length of PRSS1, cystic fibrosis transmembrane conductance regulator (CFTR), and pancreatic secretory trypsin inhibitor (SPINK1) genes mutations in an AIP family and a sporadic case and 520 normal controls. Furthermore, a mutant-expressing system was constructed for functional confirmation. RESULTS For the first time, we report a deletion mutation at exon 2 of PRSS1 gene (IVS 2 +56_60 del CCCAG) which encoded a truncated PRSS1 protein without trypsinogen activation peptide (TAP). Vitro functional study suggested the identified mutation would result in loss of PRSS1 activity. Mutant trypsinogen activated at a faster rate than wild-type trypsinogen in the autoactivation experiment. Histopathologic examination revealed the ratio of IgG4/IgG-positive plasma cells exceeded 0.455 in pancreas, and the patients responded to glucocorticoids. CONCLUSION PRSS1: IVS 2 +56_60 del CCCAG is a noval mutant which may contribute to AIP pathogenesis.