THE CYSTIC-FIBROSIS GENE, ITS MUTATIONS, AND THE CFTR PROTEIN

Cystic fibrosis is a severe inherited disease that is common in Caucasians (1 of 3 000 live births). The complex mechanisms that underlie cystic fibrosis lead to electrolyte transport disorders with insufficient secretion of chloride by various epithelia. This article briefly,reviews data collected since cloning of the cystic fibrosis gene and characterization of its protein product, the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator). The CFTR is one of several membrane-spanning proteins characterized by two ATP-binding domains, found in a number of prokaryotic and eukaryotic cells. A unique feature of the CFTR is a highly charged domain, called the R domain. The CFTR acts as a chloride channel and probably plays a role in transmembrane transportation of as yet unidentified substances. Most (70%) cystic fibrosis chromosomes exhibit deletion of a single codon for the phenylalanine in position 508 of the CFTR polypeptide chain (Delta F508). Of the more than 240 other, less common mutations that have:been identified, some are more prevalent in specific ethnic groups or geographic areas. These data, which have accumulated rapidly over the last three years, have impacted the diagnosis and prevention of cystic fibrosis and provided valuable insights into the structure and function of the CFTR.