title: Analysis of CFTR, SPINK1, PRSS1 and AAT mutations in children with acute or chronic pancreatitis.
abstract: OBJECTIVE
  Defects of PRSS1, SPINK1, CFTR and AAT are considered causative or predisposing to pancreatitis. The aim of this study was to evaluate the impact of these defects into molecular pathology of chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP).
  
  
  METHODS
  Ninety-two children with CP or ARP, 55 family members and 50 controls were investigated. The subjects were screened for PRSS1 mutations: R122H, R122C, A16V, N29I; SPINK1 N34S variant; panel of 14 CFTR defects: INNOLiPA CFTR12, CFTRdele2,3 and IVS8-T variant or panel of 3 CFTR defects-F508del, CFTRdele2,3 and IVS8-T; AAT mutations: E264V, E342K.
  
  
  RESULTS
  We identified 1 mutated allele in at least 1 of 4 genes in 31 of 92 patients and 12 of 50 controls (P = 0.157). Mutations in SPINK1 and PRSS1 were most frequent. PRSS1 mutations were identified mainly in CP patients (9.6% of CP vs 2.5% of ARP alleles, P = 0.094), whereas N34S SPINK1 mutation was present with comparable frequency in CP and ARP patients (7.7% vs 10.0%, P = 0.768). The frequency of mutations in CFTR alleles was similar to controls (4.9% vs 5%, P = 0.587). Overall frequency of AAT mutations was lower than in the controls. Family studies showed that defects in the examined genes did not always segregate with disease.
  
  
  CONCLUSIONS
  PRSS1 defects seem to be causative for pancreatitis, whereas defects in SPINK1 are suggested to be associated with the disease. No association between CFTR mutations and pancreatitis was observed. The importance of AAT variants remains speculative.
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland. agnieszka.sobczynska@imid.med.pl
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sobczyńska-Tomaszewska
authors.forename: Daniel
authors.initials: D
authors.lastname: Bak
authors.forename: Beata
authors.initials: B
authors.lastname: Oralewska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Oracz
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Norek
authors.forename: Kamila
authors.initials: K
authors.lastname: Czerska
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Mazurczak
authors.forename: Mikołaj
authors.initials: M
authors.lastname: Teisseyre
authors.forename: Jerzy
authors.initials: J
authors.lastname: Socha
authors.forename: Marek
authors.initials: M
authors.lastname: Zagulski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bal
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004247:DNA / Q000097:blood; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D010195:Pancreatitis / Q000235:genetics*; D012008:Recurrence; D014357:Trypsin; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen / Q000235:genetics*; D000515:alpha 1-Antitrypsin / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C486642:SPINK1 protein, human; D000515:alpha 1-Antitrypsin; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen; D004247:DNA; C489303:PRSS1 protein, human; D014357:Trypsin