Difference in frequencies of the cystic fibrosis alleles, delta F508 and W1282X, between carriers and patients.

One major mutation, ΔF508, causing cystic fibrosis (CF) is found in most populations around the world. Among CF patients of Jewish Ashkenazi origin two major mutations, W1282X and AF508 were found. We compared the relative frequencies of the two major mutations found in this patient population to their relative frequencies in the healthy population. The studied patient population included the entire CF Jewish Ashkenazi patient population in Israel (238 chromosomes), and a small group of Jewish Ashkenazi patients in the USA (57 chromosomes). Among these, 79 (27%) chromosomes carried the ΔF508 mutation, and 151 (51%) the W1282X mutation. In addition, we have analyzed the results of screening 1,946 unrelated healthy Jewish Ashkenazi individuals for the ΔF508 and the W1282X mutations. Surprisingly, an almost equal number of carriers of the ΔF508 (35) and W1282X (36) was found. The difference between the relative proportions of the mutations in the two groups is statistically significant (p = 0.025). A striking manifestation of this difference is revealed in the analysis of patients’ genotypes. There were 36 patients homozygous for W1282X, while only 7 patients were homozygous for ΔF508, although the number of ΔF508 carriers in the general Jewish Ashkenazi population is almost equal to the number of W1282X carriers. This difference in allele frequencies found between healthy carriers and CF patients in the Jewish Ashkenazi population might not be unique to this ethnic group nor to the CF disease. The results indicate that the common practice of inferring general population epidemiologic parameters directly from patients information is liable to introduce biases. Thus, widespread screenings should be preceded by smaller-scale pilot studies designed to verify that the mutation frequencies in the patient population represent the carrier frequencies in the relevant general population.