title: PRSS1 and SPINK1 mutations in idiopathic chronic and recurrent acute pancreatitis.
abstract: OBJECTIVE
  To identify gene mutations in PRSS1 and SPINK1 in individuals with early onset idiopathic chronic or recurrent acute pancreatitis.
  
  
  METHODS
  The cationic trypsinogen gene (PRSS1; exons 2 and 3) and the serine protease inhibitor Kazal 1 gene (SPINK1; exon 3) were selectively amplified and sequenced from blood samples of 19 patients admitted to the Pancreas Clinic at our institution with chronic pancreatitis and/or idiopathic recurrent acute pancreatitis that were diagnosed or with onset before age 35. Fifty healthy volunteers served as controls. Whole blood samples were collected and gene specific sequences were amplified by polymerase chain reaction (PCR). All PCR products were subsequently sequenced in order to identify the presence of any mutations.
  
  
  RESULTS
  Nineteen patients with pancreatitis (14 males; median age 24 years, range 15-48 years) were included in this study, of which five showed the presence of gene mutations. Direct sequencing results indicated the presence of two previously unidentified mutations in exon 2 of PRSS1 (V39E and N42S) in two patients with recurrent acute pancreatitis. Two cases had the N34S SPINK1 mutation. Analysis of the relatives of one patient homozygous for this mutation showed that five of the six family members carried the N34S SPINK1 mutation. Of these members, three were healthy heterozygous carriers and two were homozygotes (one sibling had diabetes, the other was healthy). Another patient was heterozygous for a novel SPINK1 mutation located on exon 3 (V46D). All members from this patient's family had normal genotypes, indicating that it was a de novo mutation. No mutations in either gene were present in the control subjects.
  
  
  CONCLUSIONS
  Two novel PRSS1 mutations and one novel SPINK1 mutation were identified in Mexican patients with early onset idiopathic recurrent acute pancreatitis.
authors.affiliation: Mario Pelaez-Luna, Guillermo Robles-Diaz, Research Division, School of Medicine, UNAM, Pancreas Clinic-Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, CP 14000, Mexico.
authors.forename: Mario
authors.initials: M
authors.lastname: Pelaez-Luna
authors.affiliation: Mario Pelaez-Luna, Guillermo Robles-Diaz, Research Division, School of Medicine, UNAM, Pancreas Clinic-Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, CP 14000, Mexico.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Robles-Diaz
authors.affiliation: Mario Pelaez-Luna, Guillermo Robles-Diaz, Research Division, School of Medicine, UNAM, Pancreas Clinic-Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, CP 14000, Mexico.
authors.forename: Samuel
authors.initials: S
authors.lastname: Canizales-Quinteros
authors.affiliation: Mario Pelaez-Luna, Guillermo Robles-Diaz, Research Division, School of Medicine, UNAM, Pancreas Clinic-Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, CP 14000, Mexico.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Tusié-Luna
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D010195:Pancreatitis / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D050500:Pancreatitis, Chronic / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D011446:Prospective Studies; D012008:Recurrence; D012189:Retrospective Studies; D014357:Trypsin / Q000235:genetics*; D014359:Trypsin Inhibitor, Kazal Pancreatic; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; C489303:PRSS1 protein, human; D014357:Trypsin
keywords: Cationic trypsinogen; Chronic pancreatitis; Hereditary pancreatitis; PRSS1; Recurrent acute pancreatitis; SPINK1