MUTATION ANALYSIS IN THE DIAGNOSIS OF CYSTIC-FIBROSIS

Since the characterization of the gene encoding the cystic fibrosis tr ansmembrane conductance regulator protein and identification of its ma in mutation, DELTAF508, causing cystic fibrosis (CF), more than 150 mu tations in this gene have been reported, most of them only in a few or even single CF patients. Attempts to use mutation analysis in genetic counselling or for the diagnosis of CF depends on prevalence data of certain mutations in the respective population, and considerable ethni c differences have been reported. In this study we determined the prev alence of the mutations DELTAF508, G551D, R553X, and G542X and of geno types defined by these mutations in 239 CF patients (444 independent C F chromosomes) seen in our clinic. The analysis for those four mutatio ns alone now permits identification of approximately 75% of all mutati ons in our CF patients. The complete genotype can be resolved in appro ximately 63% of patients. This represents the diagnostic sensitivity w hich can be achieved by mutation analysis in patients without a family history of CF. We conclude that in situations where conventional diag nostic tests are not feasible or difficult to interpret, mutation anal ysis using a limited set of mutations can contribute significantly to an early and specific diagnosis of CF.