Identification of a Novel Frame-Shift Mutation in PRSS1 Gene in Han Patients with Autoimmune Pancreatitis
Identification of a Novel Frame-Shift Mutation in PRSS1 Gene in Han Patients with Autoimmune Pancreatitis
复制标题
汉族自身免疫性胰腺炎患者 PRSS1 基因新移码突变的鉴定
DOI：
10.2174/1566524013666131118114432
复制
发表时间：
2014-03-01
影响因子：
2.5
通讯作者：
Xu, Z.
中科院分区：
文献类型：
--
作者：
Gao, F.;Li, Y.;Xu, Z.
目的：目的：检测自身免疫性胰腺炎（AIP）患者胰蛋白酶原基因（PRSS 1）的突变情况，探讨其发病机制。方法：应用DNA测序技术，检测1个AIP家系、1例散发病例和520例正常对照者的PRSS 1、囊性纤维化跨膜传导调节因子（CFTR）和胰腺分泌型胰蛋白酶抑制因子（SPINK 1）基因的突变情况。结果：首次发现PRSS 1基因第2外显子缺失突变（IVS 2 + 56_60 del CCCAG），编码不含胰蛋白酶原激活肽（TAP）的截短型PRSS 1蛋白。体外功能研究表明，所鉴定的突变将导致PRSS 1活性的丧失。在自激活实验中，突变型胰蛋白酶原以比野生型胰蛋白酶原更快的速率激活。组织病理学检查显示胰腺IgG 4/IgG阳性浆细胞比值> 0.455，且对糖皮质激素有反应。结论：PRSS 1：IVS 2 + 56_60 del CCCAG是一种新的突变体，可能与AIP的发病有关。
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.