DNA diagnosis of cystic fibrosis by direct detection of the delta F508 mutation.

Cystic fibrosis (CF) is one of the most frequent recessive disorders among Caucasians. DNA analysis is performed by linkage analysis with DNA markers tightly linked to the CF gene. Cloning and sequencing of the cystic fibrosis gene, however, revealed that the major disease mutation is a phenylalanine deletion at amino acid position 508 of the mature protein (delta F508). These recent discoveries open great perspectives for the diagnosis of cystic fibrosis and for the detection of carriers in the normal population. In the present study we have used the polymerase chain reaction to detect the delta F508 mutation. This mutation was present on 80.3% of the CF chromosomes in the Belgian population. Twenty-three of 740 normal individuals (3.1%) were heterozygous carriers. Therefore, the frequency of heterozygous carriers in the Belgian population is estimated to be about 3.9% or 1 in every 26 individuals.