1080

CFTR

ABC35|ABCC7|CF|CFTR/MRP|MRP7|TNR-CFTR|dJ760C5.1;cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7);CFTR;cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)

ATP-binding cassette sub-family C member 7|ATP-binding cassette transporter sub-family C member 7|cAMP-dependent chloride channel|channel conductance-controlling ATPase|cystic fibrosis transmembrane conductance regulator

7q31.2

protein-coding

Hereditary pancreatitis (HP) is an autosomal dominant disorder characterized by recurrent acute attacks of severe abdominal pain with an onset in early childhood. Many HP patients progress to complicated chronic pancreatitis and/or pancreatic cancer. Initially, a single mutation R117H in the cationic trypsinogen gene was detected in ALL affected members of five unrelated HP families. Furtherstudies identified a second mutation (N21L) in two HP families without the R117Hmutation. Before the association between cationic trypsinogen and HP was found, we detected a cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation (L327R) in ALL affected individuals of a family with HP. We therefore performed a mutational analysis for R117H and N21L in cationic trypsinogen in this and three additional unrelated families with HP. The R117H mutation was detected in ALL 9 affected members of three HP families and in 3 asymptomatic but at-risk relatives. However, neither the R117H nor the N21L mutation in the cationic trypsinogen were found in the HP family with the L327R alteration in CFTR. The L327R allele segregates with the disease within this HP family and wasnot detected on 360 unrelated Caucasian non-CF chromosomes. Although close to 800 different mutations have been detected in the CF gene of cystic fibrosis patients, L327R is a new alteration, not yet reported in connection with CF. Theresults of this study indicate that the CFTR gene may play a role in the etiology of minority of cases with HP and suggest that hereditary pancreatitis is genetically heterogeneous disease.

Hereditary pancreatitis (HP) is an autosomal dominant inherited disease characterized by recurrent episodes of pancreatitis often beginning in childhood, a family history of at least 2 other affected members, and the absence of known etiologic factors. The discovery of mutations in cationic trypsinogen gene (PRSS1) in HP not only provided insights into the molecular mechanisms of pancreatitis, but also opened a new era in the field of chronic pancreatitis. The detection of mutations in serine protease inhibitor, Kazal type 1 (SPINK1) and CFTR in patients with hereditary or idiopathic chronic pancreatitis has placed the emphasis on the importance of genetic mutations in pancreatitis. Because theestimated cumulative risk of pancreatic cancer development in hereditary pancreatitis is nearly 40%, screening tests are important in selected cases. There are no specific medical therapies recommended in patients with HP. Registration of patients with Nationwise Registries is essential if management strategies are to be improved and genetic research to be continued.#FAU - Kim, Yong-Tae