Cystic fibrosis: From gene discovery to precision medicine

Abstract

The discovery in 1989 that cystic fibrosis, the most common life-shortening hereditary disease in Caucasians, was caused by mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene, put in motion whole new areas of research, diagnosis, and therapeutic development. In this review, we focus on the most important advances in our understanding of the molecular basis of CFTR dysfunction. To date, over 2,000 CFTR mutations belonging to six protein-defect classes have been identified, increasing vastly our understanding of genotype/phenotype correlations. In the last 30 years, major achievements have been made in neonatal screening, antenatal diagnosis, and crucially with recent breakthroughs in the development of CFTR-directed therapies that may be effective for 90% of patients, paving the way for precision medicine.