Genetic characterization of cystic fibrosis patients in Russian Federation according to the National Register, 2014

Красовский, С. А.; Каширская, Н. Ю.; Черняк, А. В.; Амелина, Е. Л.; Петрова, Н. В.; Поляков, А. В.; Kondratyeva, E.I.; Воронкова, А. Ю.; Usacheva, M.; Адян, Т. А.; Степанова, Анна; Алимова, И Л; Asherova, I.; Байкова, Г. В.; Басилая, А. В.; Бойцова, Е В; Борисов, А. В.; Brisin, V.; Васильева, Е. А.; Васильева, Т. Г.; Vodovozova, Ella; Воронин, С. В.; Гаймоленко, И. Н.; Golubtsova, O.; Горинова, Ю. В.; Назаренко, Л. П.; Odinokova, O.; Гембицкая, Т. Е.; Nikonova, V.; Дьячкова, А. А.; Sergienko, D.F. Sergienko; Енина, Е. А.; Erzutova, M.; Зинченко, Ю. С.; Zonenko, O.; Ivanova, D.; Ильенкова, Н. А.; Kadyrova, D.V.

doi:10.18093/0869-0189-2016-26-2-133-151

Cited by 5 publications

(2 citation statements)

References 8 publications

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“…The CF frequency in European countries is 1 per 2500–4500 newborns on average, and in Russia it is about 1 per 10,000 newborns [ 6 , 7 ]. According to the Russian Cystic Fibrosis Patient Registry 2018 (RCFPR), more than 200 pathogenic variants of the CFTR gene have been identified in the Russian Federation, the most frequent being eleven variants: c.1521_1523delCTT (p.Phe508del, F508del)—53.05%; c.54-5940_273+10250del21kb (p.Ser18Arg*fsX16, CFTRdele2,3)—6.09%; c.274G>A (p.Glu92Lys, E92K)—3.04%; c.3718-2477C>T (3849+10kbC-T)—2.38%; c.2012delT (p.Leu671X, 2143delT)—2.11%; c.2052_2053insA (p.Gln685ThrfsX4, 2184insA)—1.84%; c.3846G>A (p.Trp1282X, W1282X)—1.75%; c.1545_1546delTA (p.Tyr515X, 1677delTA)—1.77%; c.3909C>G (p.Asn1303Lys, N1303K)—1.55%; c.1624G>T (p.Gly542X, G542X)—1.48%; and c.413_415dupTAC (p.Leu138dup; L138ins)—1.35% [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical Presentation of the c.3844T>C (p.Trp1282Arg, W1282R) Variant in Russian Cystic Fibrosis Patients

Петрова

Kashirskaya

Krasovskiy

et al. 2020

Genes

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The goal was to study the phenotypic manifestations of c.3844T>C (p.Trp1282Arg, W1282R) variant, a CF-causing mutation, in patients from the Russian Federation. Clinical manifestations and complications (the age at CF diagnosis, sweat test, pancreatic status, lung function, microbial infection, body mass index (BMI), the presence of meconium ileus (MI), diabetes, and severe liver disease) were compared in four groups: group 1—patients carrying c.3844T>C and severe class I or II variant in trans; group 2—3849+10kbC>T/F508del patients; group 3—F508del/F508del patients; and group 4—patients with W1282R and “mild” variant in trans. Based on the analyses, W1282R with class I or II variant in trans appears to cause at least as severe CF symptoms as F508del homozygotes as reflected in the early age of diagnosis, high sweat chloride concentration, insufficient pancreatic function, and low lung function, in contrast to 3849+10kbC-T/F508del compound heterozygotes having milder clinical phenotypes. The W1282R pathogenic variant is seemed to lead to severe disease phenotype with pancreatic insufficiency similarly to the F508del homozygous genotype.

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Section: Introductionmentioning

confidence: 99%

Clinical Presentation of the c.3844T>C (p.Trp1282Arg, W1282R) Variant in Russian Cystic Fibrosis Patients

Петрова

Kashirskaya

Krasovskiy

et al. 2020

Genes

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“…Клиническая гетерогенность МВ в значительной степени зависит от «тяжести» мутаций CFTR [ 15 ]. Мутации класса I определяют полную блокаду синтеза CFTR, обнаруживаются в 2–5% случаев МВ во всем мире.…”

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Cystic fibrosis being a polyendocrine disease (Review)

Chagay

Khayt

Вдовина

et al. 2021

Probl Endokrinol (Mosk)

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The cystic fibrosis transmembrane regulator (CFTR) gene encodes the synthesis of a protein of the same name, which functions as a direct activator of anionic transport. Chloride is the most abundant anion; as an antagonist of Na+ and K+, it provides electroneutrality of cell membranes at rest; together with cations, it serves as an important osmolyte and forms water flow across cell membranes for transepithelial secretion.Glandular cells in CF trap Cl– and Na+, and the prodused secretion is excessively viscous. Subnormal CFTR activity leads to stagnation of mucociliary clearance, inhibition of intestinal transport.In addition to exocrine disorders, CFTR mutations are associated with a decrease in volume, mass, increased apoptosis of β-cells of the pancreas, a significant suppression of insulin exocytosis in response to stimulation with glucose and glucagon-like peptide-1, hyperglucagonemia against the background of a defect in the suppression of α-cell function by insulin, but a decrease in maximum capacity α-cells.Deficiency and progressive decline in bone mineral density is an expected secondary manifestation of CF due to pancreatic exocrine insufficiency with malabsorption of nutrients and fat-soluble vitamins. However, in patients with the F508del mutation, a significant decrease in the synthesis of OPG, COX-2, PGE2 in the osteoblastic formation, and an increase in the activity of the antianabolic NF-kB were found. We are talking about a defect in the canonical signaling pathway (Wnt/β-catenin), which regulates the expression of genes-activators of osteoblastogenesis, dissociation of the stages of physiological bone remodeling.In addition to congenital bilateral or unilateral aplasia of the vas deferens, an increase in the frequency of CFTR mutations is also found in non-obstructive azoospermia, oligo-, astheno- and teratospermia. CFTR is involved in the entry of HCO3– into Sertoli cells to trigger cAMP-dependent transcription and its defects lead to suppression of FSH-dependent gene expression of spermatogenesis, loss of sequence in the Wnt cascade, destruction of the PGE2-dependent transepithelial interaction and, as a consequence, the blood-testicular barrier.CF is characterized, along with classical signs, by endocrine dysfunction of the pancreas, osteoporosis with suppression of osteoblastogenesis, and a defect in spermatogenesis.

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