CYSTIC-FIBROSIS - THE IMPACT OF ANALYTICAL TECHNOLOGY FOR GENOTYPE-PHENOTYPE STUDIES

The generalized exocrinopathy cystic fibrosis (CF) is the most common severe genetic disease in Caucasian populations. A panel of more than 700 chromosomes from German and Turkish CF patients was screened for d isease-causing mutations in the cystic fibrosis transmembrane conducta nce regulator (CFTR) gene by chemical cleavage of mismatch, single str and conformation polymorphism, restriction analysis and direct sequenc ing of genomic DNA amplified by polymerase chain reaction. Besides the major 3-bp deletion, DELTAF508 that was found on 73% of German CF chr omosomes, more than 50 other missense, nonsense, frame-shift, and spli ce-site mutations have already been identified. In general, a CFTR mut ation is linked with a single 10-marker haplotype which indicates that in most cases a particular mutation spread from a common ancestor. Th e comparison of mutation genotypes with the disease phenotype emphasiz ed the causative role of the type and localization of the CFTR mutatio n for clinical course and prognosis. Pancreatic status and the risk of colonization of airways with opportunistic pathogens are genetically determined. Most patients who are harbouring mutations in the nucleoti de binding folds were suffering from severe CF disease. Mild or even a berrant forms of CF were observed for many missense mutations located in the putative transmembrane domains or for mutations that are expect ed to result in a truncated protein of half of wild-type CFTR.