Signal peptide variants that impair secretion of pancreatic secretory trypsin inhibitor (SPINK1) cause autosomal dominant hereditary pancreatitis

PATHOBIOCHEMISTRY OF PANCREATIC SECRETORY TRYPSIN INHIBITOR (SPINK1) Extract of PhD dissertation

Absence of PRSS1 mutations and association of SPINK1 trypsin inhibitor mutations in hereditary and non-hereditary chronic pancreatitis.

BACKGROUND AND AIMS Mutations in the cationic trypsinogen (protease, serine, 1 (trypsin 1); PRSS1) gene are causally associated with recurrent acute and chronic pancreatitis. We investigated whether mutations in the PRSS1 gene are associated with hereditary and non-hereditary pancreatitis. As a modifier role has been proposed for trypsin inhibitor (serine protease inhibitor, Kazal type I; SPINK...

Application of proteomic technology in identifying pancreatic secretory trypsin inhibitor variants in urine of patients with pancreatitis.

BACKGROUND Although the analysis of genetic variability has traditionally been performed with molecular genetic techniques, the development of proteomic technology has raised the possibility of analyzing genetic variants at the protein level. This method provides additional information about posttranslational modifications and differences in expression. We used mass spectrometry to characterize...

From acute to chronic pancreatitis: the role of mutations in the pancreatic secretory trypsin inhibitor gene.

Pancreatic secretory trypsin inhibitor (PSTI) is a potent natural inhibitor of trypsin. We proposed the hypothesis that, if the function of the PSTI is impaired by its genetic mutation, trypsin may easily promote autodigestion causing pancreatitis and we performed a mutational analysis of the PSTI gene in patients with pancreatitis. Two exonic mutations (N34S and R67C) were thought to be associ...

Novel cationic trypsinogen (PRSS1) N29T and R122C mutations cause autosomal dominant hereditary pancreatitis.

Hereditary pancreatitis (HP) is usually caused by mutations in the cationic trypsinogen (PRSS1) gene, especially R122H or N29I. We sequenced the PRSS1 gene in the proband of families without these common mutations. Novel R122C and N29T mutations were detected in independent families that segregated with the disease in an autosomal dominant fashion. The R122C mutation eliminates the arginine aut...