Mutations of the cystic fibrosis gene, but not cationic trypsinogen gene, are associated with recurrent or chronic idiopathic pancreatitis

OBJECTIVE: We investigated whether mutations of the cystic fibrosis transme mbrane conductance regulator (CFTR) gene and cationic trypsinogen gene are associated with recurrent acute, or chronic idiopathic pancreatitis. METHODS: Twenty patients with idiopathic pancreatitis (11 women, nine men; mean age, 30 yr) were studied for the presence of a CFTR mutation by screen ing the genomic DNA for more than 30 mutations and variants in the CFTR gen e. Selected mutations of the cationic trypsinogen gene were screened by Afl III restriction digestion or by a mutation-specific polymerase chain react ion (PCR). In each patient exons 1, 2, and 3 of the cationic trypsinogen ge ne were sequenced. Patients with a CFTR mutation underwent evaluation of fu rther functional electrophysiological test (intestinal current measurement) . RESULTS: No mutation of the cationic trypsinogen gene was detected. A CFTR mutation was detected in 6/20 (30.0%) patients. Three patients (15.0%) had a cystic fibrosis (CF) mutation on one chromosome (Delta F508, I336K, Y1092 X), which is known to cause phenotypical severe cystic fibrosis. One patien t was heterozygous for the 5T allele. In addition, two possibly predisposin g CFTR variants (R75Q, 1716G-->A) were detected on four patients, one of th ese being a compound heterozygous for the missense mutation I336K and R75Q. No other family member (maternal I336K; paternal R75Q; sister I1336K) deve loped pancreatitis. An intestinal current measurement in rectum samples of patients with a CFTR mutation revealed no CF-typical constellations. CONCLUSIONS: CFTR mutations are associated with recurrent acute, or chronic idiopathic pancreatitis, whereas mutations of the cationic trypsinogen mut ation do not appear to be a frequent pathogenetic factor. (C) 2000 by Am. C ell. of Gastroenterology.