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

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.

journal_name

Curr Mol Med

authors

Gao F,Li Y,Wang C,Zhuang Z,Liu QC,Chen J,Hong G,Xu Z

doi

10.2174/1566524013666131118114432

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

340-8

issue

3

eissn

1566-5240

issn

1875-5666

pii

CMM-EPUB-57463

journal_volume

14

pub_type

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