High frequency of complex CFTR alleles associated with c.1521_1523delCTT (F508del) in Russian cystic fibrosis patients

• Published in: BMC genomics Vol. 23; no. 1; p. 252
• Main Authors: Petrova, Nika V, Kashirskaya, Nataliya Y, Vasilyeva, Tatyana A, Balinova, Natalia V, Marakhonov, Andrey V, Kondratyeva, Elena I, Zhekaite, Elena K, Voronkova, Anna Y, Kutsev, Sergey I, Zinchenko, Rena A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01-04-2022; BioMed Central; BMC
• Subjects: Alleles; Allelomorphism; CFTR; Chromosomes; Cis-mutation; Complex alleles; Cystic fibrosis; Cystic Fibrosis - genetics; Cystic fibrosis transmembrane conductance regulator; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Disease; Epistasis; Feces; Gene frequency; Gene mutations; Genetic aspects; Genetic diversity; Genetic variance; Genomics; Genotypes; Haplotypes; Health services; Homozygote; Humans; Medical research; Medicine, Experimental; Modulators; Mutation; Patients; Peptides, Cyclic - metabolism; Polymorphism; Risk factors; Russian patients; Russia; Cis-mutation; Cystic fibrosis; Russian patients; CFTR; Complex alleles
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-022-08466-z

Cystic fibrosis (CF, MIM# 219,700) is an autosomal recessive disease caused by pathogenic variants within the CFTR gene. It was shown that genetic variants located in cis can affect disease severity or treatment response because of additive or epistatic effects. Studies on the prevalence of complex alleles in Russian CF patients have just begun. Aim To evaluate frequencies and genetic background of complex alleles carrying c.1521_1523delCTT (F508del) and c.1399C>T (L467F), c.2562T>G (T854=) or c.4389G>A (Q1463=) in cis; to determine clinical consequences of complex allele c.[1399C>T;1521_1523delCTT] ([L467;F508del]) in Russian CF patients. Methods Sequencing of coding regions of CFTR gene and analysis of polymorphic markers in CF patients carrying F508del variant. Comparing of clinical features in two groups patients having genotypes [L467F;F508del];[F508del] (group 1) and [F508del];[F508del] (group 2). Results Frequency of [L467F;F508del] allele linked to 2-2-21-6-17-13 haplotype was 4.42%, of [F508del;T854=;Q1463=] allele linked to haplotype 1-2-21-6-17-13 - 2.2% in F508del chromosomes. No differences in disease severity in patients carrying complex allele [L467F;F508del] and patients homozygous for F508del was found. Conclusion The frequency of complex alleles associated with F508del was at least 6.6% in Russian CF patients, which should be taken into account for the decision on optimal treatment options with CFTR modulators.