DETECTION OF MORE THAN 50 DIFFERENT CFTR MUTATIONS IN A LARGE GROUP OF GERMAN CYSTIC-FIBROSIS PATIENTS

We have conducted a comprehensive study of the molecular basis of cyst ic fibrosis (CF) in 350 German CF patients. A screening approach based on single-strand conformation analysis and direct sequencing of genom ic polymerase chain reaction products has allowed us to detect the mol ecular defects on 95.4% of the CF chromesomes within the coding region and splice sites of the cystic fibrosis transmembrane conductance reg ulator (CFTR) gene. The spectrum of sequence changes comprises 54 diff erent mutations, including 17 missense mutations, 14 nonsense mutation s, 11 frameshift mutations, 10 splice site variants and two amino acid deletions. Eleven of these mutations have not previously been describ ed. Our results reflect the marked mutational heterogeneity of CF in a large sample of patients from a non-isolated population.