THE CYSTIC-FIBROSIS GENE, THE CFTR AND IT S MUTATIONS

Cystic fibrosis (CF) is a fatal genetic disease primarily affecting Ca ucasians. Its etiology is complex, but it is chiefly a disease of elec trolyte transport characterized by defects in fluid secretion by sever al epithelia. In this review are analyzed the data obtained since the cloning of the CF gene and the characterization of its product, the CF transmembrane conductance regulator (CFTR) protein, which has been sh own to act like a cAMP-regulated chloride channel. This protein is a m ember of a family of ATP-binding proteins that are membrane-spanning, are found in a number of prokaryotic and eucaryotic cells, and have tw o ATP-binding domains. Unique to this family of proteins, the CFTR pos sesses an additional highly charged domain (the R domain). The majorit y of CF chromosomes (70 %) have a single Phenylalanine codon deletion at position 508 of the protein (DELTAF508). A large number of other ra re mutations (more than 230) have also been identified. This rapid acc umulation of data is essential to genetic diagnosis and will aid in un derstanding the structure and function of the protein.