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. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.