Since the beginning of the program for molecular characterization of CF in Macedonia in 1989, a total of 228 unrelated patients suspected for the disease were referred for genetic testing to the laboratory of the RCGEB, MASA, Skopje, Republic of Macedonia. The main indications for referral were chronic pulmonaly disease and initial positive sweat test. Over the years, 107 patients were excluded from the CF registry, and from the program for detailed molecular analysis because of the lack of a positive sweat test on three consecutive tests, and of the disappearance of symptoms with advanced age of the patients.

      Table 1 summarizes the results on the frequencies of different CFTR gene mutations found in 121 patients who remained in the CF Registry in the Republic of Macedonia. A total of 13 different mutations were detected, the most frequent being DF508 (62.4%), followed by G542X (5.3%), N1303K (2.2%) CFTRdele21kb (1.6%), 621+1G?T (1.3%), 711+3A®G (0.9%), 3849G®A (0.9%), 457TAT®G (0.9%), V1397E (0.9%), 2184insA (0.9%) 1811+1G®C (0.4%), 2789+5G®A (0.4%), and Y569C (0.4%). Four of the mutations (711+3A®G, 1811+1G®C, V1397E and Y569C) were described for the first time [21-24]. The DF508 mutation showed a higher incidence among Macedonians (67.8%) than among Albanians (58.1%) living in Republic of Macedonia (Table 2). The observed difference does not reach statistical significance. During this study eight known (R75Q, 405+46G/T, 875+40A/G, L467P, M470V, T966T, 3041-92G/A and 4002A/G), and one new (P324P) polymorphism in the CFTR gene were found [25].

      Thirty-one prenatal diagnoses were performed in 31 families at-risk for a child with CF (Table 3). In eight fetuses the analysis showed absence of mutation on both chromosomes, 17 fetuses were carriers, while six fetuses were affected with CF. In all instances the results were confirmed after birth or after termination of pregnancy.

 Table 1. Frequency of different CF mutations identified in patients from the Republic of Macedonia