Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is an autosomal recessive inherited disorder caused by mutations of both alleles of the CF gene. These mutations result in abnormalities in the production or function of the gene product, a protein known as the cystic fibrosis membrane conductance regulator (CFTR). The CF gene is large (250 000 base pairs) and located on chromosome 7. A deletion of three base pairs that results in the absence of phenylalanine at codon 508 is the most common defect (designated F 508) and accounts for about 70% of the mutant genes in North American populations. Other genotypes observed with some frequency (but <3%) are G542X, G551D, W1282X, W1303K, and R553X. The twelve most common CF gene mutations account for approximately 85% of cases in North America. Mutations other than F508 number more than 200 and account for the remaining cases. Most of these 200-odd mutations are "private," observed only in the affected kindred. Because the CF locus has so many DNA sequence changes associated with disease, precise genetic testing cannot replace clinical criteria for diagnosis, and the sweat test remains an important diagnostic test. The CF gene is expressed in epithelial cells of the pancreas, sweat and salivary glands, intestine, and reproductive and respiratory tracts, particularly in the submucosal glands.