[DNA analysis and gene diagnosis of cystic fibrosis]

Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population, affecting approximately 1 in 2,000 newborns but the actual estimate varies with the geographic location. The incidence of CF in non-Caucasian populations is low. Intensive efforts using genetic linkage information ultimately led to the cloning of the CF gene prior to the identification of the gene product or its function. The gene encodes what is believed to be a transmembrane protein, which has been named the cystic fibrosis transmembrane conductance regulator (CFTR). The CFTR contains two nucleotide-binding folds (NBF) which show homology to numerous transport proteins with the greatest homology to the P-glycoproteins that are encoded by the multiple drug-resistance loci. A three- base deletion resulting in the loss of phenylalanine residue (delta F508) in the tenth exon of the CFTR gene is the mutation occurring on the majority of CF chromosomes. The overall frequency of delta F508 in the present mutant CF gene pool is about 70%, but the study populations are not equally represented: there is marked variation in the population of delta F508 among different geographic populations. Recently, numerous additional, less common mutations have been found. Some mutations occur on 2-5% of the CF chromosomes. Many of these are rare 'private' mutations, occurring in individual families of all racial and ethnic backgrounds. By contrast over 80% of Western European CF mutations have been identified. The highly heterogeneous nature of the remaining CF mutations provides important insights into the structure and function of the protein, but further improvements are needed in DNA-based genetic screening for CF carrier status.