Cystic Fibrosis Polymorphic Variants in a Russian Population
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Anna Kiseleva,1,* Marina Klimushina,1,* Evgeniia Sotnikova,1,* Olga Skirko,1 Mikhail Divashuk,1,2 Olga Kurilova,1 Alexandra Ershova,1 Eleonora Khlebus,1 Anastasia Zharikova,1,3,4 Irina Efimova,1 Maria Pokrovskaya,1 Petr A Slominsky,5 Svetlana Shalnova,1 Alexey Meshkov,1,* Oxana Drapkina1,* 1Federal State Institution «National Medical Research Center for Therapy and Preventive Medicine» of the Ministry of Healthcare of the Russian Federation, Moscow, 101000, Russia; 2Kurchatov Genomics Center-ARRIAB, All-Russia Research Institute of Agricultural Biotechnology, Moscow 127550, Russia; 3Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119991, Russia; 4Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow 127051, Russia; 5Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, Russia*These authors contributed equally to this workCorrespondence: Anna Kiseleva Email sanyutabe@gmail.comPurpose: Cystic fibrosis (CF) is one of the most common monogenic diseases with an autosomal recessive inheritance. Carrier screening leads to a reduction in the number of children born with CF disease. The aim of this study was to develop the custom panel for the diagnosis of heterozygous carriage of polymorphic variants in the CFTR gene and to establish their allelic frequencies (AF) in one of the Russian regions where ethnic Russians predominate.Patients and Methods: The diagnostic panel was designed on the basis of data from the register of CF patients in Russia for 2017 and validated on 22 blood samples of patients with previously genetically established CF. The study participants (n=642) for CF variants estimation were randomly selected from the population-based cohort study ESSE-Vologda. Genotypes were determined by real-time PCR on the QuantStudio 12K Flex Real-Time PCR System. Data processing was performed using the TaqMan Genotyper Software.Results: The proposed diagnostic panel allowed simultaneous analysis of 60 variants of the CFTR gene. A total of 23 carriers of the following variants were identified among 642 participants: F508del (rs113993960) with a frequency of 2.02%, L138ins (rs397508686) and 394delTT (rs121908769) – 0.47%, CFTRdele2.3 (c.54– 5940_273+10250del21080; p.S18Rfs*16) – 0.31%, R117H (rs78655421), and G542X (rs113993959) – 0.16%. The frequency of heterozygotes in the Russian population was 3.58% or 1:28 (CI95%: 2.28– 5.33% by Clopper–Pearson exact method).Conclusion: High frequency of heterozygous CFTR variants carriers and availability of highly productive diagnostic panel for detection of CFTR variants suggest the prospect of carrier screening for some common CF variants among Russian population.Keywords: cystic fibrosis, CFTR, genetic analysis, carrier screening, carrier testing
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