DETECTION OF CFTR MUTATIONS IN CHILDREN WITH CYSTIC FIBROSIS

Cystic fibrosis (CF) is one of the most common monogenic disorders of humans. The knowledge of population frequency of a mutant genotype causing a monogenic disease helps to optimize DNA testing and to reduce its costs and time required for the procedure. This article presents the results of a retrospective study of the CFTR gene in 191 children with mixed manifestations of CF. To screen for 24 most common mutations, we used the diagnostic PCR panel; minor mutations were detected by next generation sequencing. The diagnostic panel allowed us to identify 18 typical CFTR mutations, including F508del (allelic frequency of 54.7%), dele 2,3 (21kb) (7.3%), 2143delT (3.4%), 2184insA (3.4%), 1677delTA (2.4%), N1303K (2.1%), 3849+10kbC>T (2.1%), E92K (2.1%), G542X (1.6%), W1282X (1.6%), S1196X (1.3%), R334W (1.0%), 394delTT(0.8%), 3944delGT (0.8%), 3821delT (0.5%), 2789+5G>A (0.5%), 621+1G>T(0.3%), and 2183AA>G (0.3%). Sequencing revealed the presence of 24 potentially pathogenic CFTR variants in the sample. We also discovered 8 minor CFTR variants previously unseen in Russian patients with CF, including 4 new CFTR mutations: p.Glu819Ter, p.Gln378Ter, p.Val1360Phefs, and p.Lys1365Argfs.