Trypsinogen gene deletion mutation causes early onset autoimmune related pulmonary bulla, hepatic multiple cysts

doi:10.3969/j.issn.1674-7151.2014.02.002

Abstract：Objective To identification of cationic trypsinogen(PRSS1) gene deletion mutation in au-toimmune related multiple cysts and its pathogenic mechanism. Methods All exons and flanking intron shear region of pancreatitis and polycystic lesions related genes including PRSS1 , cystic fibrosis transmembrane conductance regulator (CFTR), serine protease inhibitor Kazal type 1 (SPINK1), protein kinase D1(PKD1) and PKD2 were analyzed by DNA sequencing technology. The sequential variation of DNA and cDNA were de-tected. Whether the variation associated with disease were detected by comparing with family inside and healthy controls. The mutant expression system was constructed and its functional verification was done. At the same time, immunohistochemical and special staining in patients with lung and liver pancreas biopsy samples were executed. Results In two patients with autoimmune pancreatitis, deletion mutant in exon 2 of PRSS1 gene were first found, and it generating activation peptide deletion trypsinogen with biological activity. The liv-er, lung was lymphocytic and plasma cell infiltration, elastic fibers and reticular fibers decreased the formation of multiple organ polycystic disease. Serum trypsin, elastase and alpha antitrypsin increased significantly. Use of glucocorticoid treatment was effective. Conclusion PRSS1:c.1300_1304 del CCCAG is a new mutation causes early onset of autoimmune pancreatitis and it correlated with multiple organ cyst closely.