Identification of a Novel Frame-Shift Mutation in PRSS1 Gene in Han Patients with Autoimmune Pancreatitis

Title:Identification of a Novel Frame-Shift Mutation in PRSS1 Gene in Han Patients with Autoimmune Pancreatitis

Volume: 14 Issue: 3

Author(s): F. Gao, Y. Li, C. Wang, Z. Zhuang, Q.C. Liu, J. Chen, G. Hong and Z. Xu

Affiliation:

Keywords: Autoimmune pancreatitis, IVS 2 +56_60 del CCCAG mutation, molecular mechanism, PRSS1 gene.

Abstract: 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.

Cite this article as:

Gao F., Li Y., Wang C., Zhuang Z., Liu Q.C., Chen J., Hong G. and Xu Z., Identification of a Novel Frame-Shift Mutation in PRSS1 Gene in Han Patients with Autoimmune Pancreatitis, Current Molecular Medicine 2014; 14 (3) . https://dx.doi.org/10.2174/1566524013666131118114432