title: Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis.
abstract: Ten years ago, the groundwork for the discovery of the genetic basis of chronic pancreatitis was laid by linkage analyses of large kindreds with autosomal dominant hereditary chronic pancreatitis. Subsequent candidate gene sequencing of the 7q35 chromosome region revealed a strong association of the c.365G > A (p.R122 H) mutation of the PRSS1 gene encoding cationic trypsinogen with hereditary pancreatitis. In the following years, further mutations of this gene were discovered in patients with hereditary or idiopathic chronic pancreatitis. In vitro the mutations increase autocatalytic conversion of trypsinogen to active trypsin and thus probably cause premature, intrapancreatic trypsinogen activation in vivo. The clinical presentation is highly variable, but most affected mutation carriers have relatively mild disease. In this review, we summarize the current knowledge on trypsinogen mutations and their role in pancreatic diseases.
authors.affiliation: Medizinische Klinik und Poliklinik II, Universität Leipzig, Germany. niels.teich@medizin.uni-leipzig.de
authors.forename: Niels
authors.initials: N
authors.lastname: Teich
authors.forename: Jonas
authors.initials: J
authors.lastname: Rosendahl
authors.forename: Miklós
authors.initials: M
authors.lastname: Tóth
authors.forename: Joachim
authors.initials: J
authors.lastname: Mössner
authors.forename: Miklós
authors.initials: M
authors.lastname: Sahin-Tóth
mesh_terms: D004252:DNA Mutational Analysis; D030561:Databases, Nucleic Acid; D005785:Gene Conversion; D006579:Heterozygote; D006801:Humans; D020125:Mutation, Missense; D009842:Oligopeptides / Q000235:genetics; D050500:Pancreatitis, Chronic / Q000175:diagnosis* / Q000235:genetics*; D019683:Penetrance; D014357:Trypsin; D014362:Trypsinogen / Q000235:genetics* / Q000378:metabolism
chemical_list: D009842:Oligopeptides; C080396:trypsinogen activation peptide; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin