[Cystic fibrosis: molecular genetics and new perspectives of prevention and therapy]

Abstract

Cystic fibrosis (CF) is the most common lethal autosomal recessive disorder among Caucasians, occurring with a frequency of 1/2000 newborn babies. This editorial will consider the clinical features of CF as well as the genomic structure of the CFTR gene and the functional properties of its product, mutations of the gene, correlations between genotypes and phenotypes, strategies for carrier screening, and recent advances in gene therapy. After isolation and cloning of the CFTR gene, different laboratories have characterized over 350 mutations responsible for CF, the most frequent being the delta F508 which accounts for 70% of all CF chromosomes. Studies on correlations between genotypes and phenotypes have confirmed that patients with the homozygous delta F508/delta F508 genotype are severely affected, with major involvement of pancreatic function. Patients with the delta F508/R117H genotype, on the other hand, evidence a mild phenotype with pancreatic sufficiency. Several pilot studies for carrier detection are now in progress. As recent experiments with somatic gene therapy, performed on knock-out mice for the CFTR gene have given satisfactory results, it is hoped that the same approach can soon be used for humans.