Several literature reports have drawn the attention to the existence of CF alleles that carry, at the same time, the classical mutation and some of the polymorphic sites [3,4].

Both of our CF patients with alleles that have two genetic changes, have clear clinical features of disease. The one with genotype DF508/G542X+F508C has a milder form of CF, and the one with genotype DF508/ G542X+P1290P has a more severe form, accompanied by chronic airway infection. The first patient, with two genetic changes in exons that code for NBD1, had significantly higher sweat Cl– values than the second patient with the variations in the sequence for both NBDs (exons 10, 11 and 20) of the CFTR protein. These differences in the clinical feature of our patients could be result of the different genotypes, better to say different polymorphisms, considering that the mutations were the same in both cases. When sequence variations were in the part of the gene that code for the NBD1 domain (exons 9-12), clinical features were milder. A more severe clinical manifestation was present when exons for both NBD domains were mutated: exons 10 and 11 for NBD1 and exon 20 for NBD2. Thus, a deviation from a wild type of both NBD protein domains could be a reason for a more severe form of cystic fibrosis.

Considering that we found only one patient for each of the genotypes described, we cannot make certain conclusions. However, it would be interesting to combine our data with other scientists worldwide, and try to find answers about the influence of polymorphisms on the clinical features of CF patients.