Cystic Fibrosis

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (1,2). More than 1000 disease mutations and 200 polymorphisms have been identified in the CFTR gene (3). The type and frequency of mutations is very variable from ethnic population to population (4). The most common mutation, F508del (e.g., ΔF508 according to the old nomenclature), reaches frequencies of about 70% in Northern European populations. Besides F508del, other common mutations exist in most populations, each reaching frequencies of approx 1–2%. Examples include the 1717-1G→A, G542X, G551D, R553X, W1282X, and N1303K mutations. Finally, for a given ethnic population, “ethnic-specific” mutation(s) that reach frequencies of more than 1–2% might exist. For most ethnic populations, “common” mutations cover about 85% of all mutant CFTR genes. The remaining group of mutant CFTR genes in a particular ethnic population comprises rare mutations, some of them only found in a single family. Moreover, when one of the more common mutations is not found in a patient, a mutation is likely to be present that has never been detected before in that ethnic population. It is therefore very difficult to set up a strategy for a general screening of CFTR mutations, which allow sensitivities close to 100%, even in a well-characterized ethnic population.