Detection of CFTR mutations in children with cystic fibrosis

About authors

1 DNA-Technology LLC, Moscow, Russia

2 Russian Children's Clinical Hospital,
Pirogov Russian National Medical Research University, Moscow

3 Laboratory of Molecular Genetic Methods,
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow

Correspondence should be addressed: Alena I. Nikiforova
Kashirskoe shosse 24, Moscow, 115478; ur.ygolonhcet-and@avorofikin

About paper

Conflict of interests: the study was conducted in collaboration with DNA-Technology staff.

Received: 2018-07-10 Accepted: 2018-08-03 Published online: 2018-08-23

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.

Keywords: Russian population, cystic fibrosis, CFTR, CFTR mutations