胰蛋白酶原
突变
外显子
自身免疫性胰腺炎
发病机制
胰腺炎
突变体
囊性纤维化跨膜传导调节器
基因
癌症研究
基因突变
分子生物学
医学
生物
遗传学
胰蛋白酶
病理
内科学
生物化学
酶
作者
Feng Gao,Y. Li,C. Wang,Zhicheng Zhuang,Q.C. Liu,J. Chen,Gwan Ui Hong,Zhiyong Xu
出处
期刊:Current Molecular Medicine
[Bentham Science]
日期:2014-03-31
卷期号:14 (3): 340-348
被引量:13
标识
DOI:10.2174/1566524013666131118114432
摘要
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. Keywords: Autoimmune pancreatitis, IVS 2 +56_60 del CCCAG mutation, molecular mechanism, PRSS1 gene.
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