Mutation analysis in the diagnosis of cystic fibrosis

Since the characterization of the gene encoding the cystic fibrosis transmembrane conductance regulator protein and identification of its main mutation, ΔF508, causing cystic fibrosis (CF), more than 150 mutations 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 ethnic differences have been reported. In this study we determined the prevalence of the mutations ΔF508, G551D, R553X, and G542X and of genotypes defined by these mutations in 239 CF patients (444 independent CF chromosomes) seen in our clinic. The analysis for those four mutations alone now permits identification of approximately 75% of all mutations in our CF patients. The complete genotype can be resolved in approximately 63% of patients. This represents the diagnostic sensitivity which can be achieved by mutation analysis in patients without a family history of CF. We conclude that in situations where conventional diagnostic tests are not feasible or difficult to interpret, mutation analysis using a limited set of mutations can contribute significantly to an early and specific diagnosis of CF.