Frequency of the delta Phe508 mutation and correlation with XV.2c/KM-19 haplotypes in an American population of cystic fibrosis patients: results of a collaborative study.

The cystic fibrosis (CF) gene has been recently cloned, and a deletion of 3 basepairs (bp) of DNA was found on most of the CF chromosomes. This deletion leads to the synthesis of a protein that lacks a phenylalanine residue at position 508. Using two polymerase chain reaction protocols to study the frequency of this mutation in a series of 192 CF patients, we found the mutation on 72% of affected chromosomes. We then used this value to calculate the predictive value of a negative test result in a population-based screening program for CF carrier status. Haplotype analysis with the polymorphic markers XV.2c and KM-19 on 239 CF chromosomes revealed that 90.7% of CF chromosomes with the deletion had a single haplotype. This haplotype was also associated with 60.4% of CF chromosomes with unknown mutations. These values can be used to calculate the probability of whether an individual from the general population is a carrier of any CF mutation.