Features of cystic fibrosis in the Chuvash Republic

Golubtsova, O.; Красовский, С. А.; Pavlov, P.; Поляков, А. В.; Степанова, Анна; Usacheva, M.

doi:10.18093/0869-0189-2013-0-3-80-88

Cited by 3 publications

(1 citation statement)

References 7 publications

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“…At the same time, some authors refer to E92K as a pathogenic variant of class IV-V [ 28 ]. Russian studies have shown that in patients homozygous and heterozygous for the E92K variant, the function of the pancreas is preserved, and therefore genotypes with the E92K variant were classified as “mild” [ 29 ]; meanwhile, there is information on the CFTR2 international project that 53% of patients with E92K have pancreatic insufficiencies [ 13 ]. According to the data of patients with CF in the Russian Federation and Turkey (2020), pancreatic insufficiency developed in 25% of E92K homozygotes, in 23.7% of patients with the E92K/F508del genotype, and in 20% of patients with the E92K/IV-VI class genotype, which is significantly lower than indicated in the CFTR2 database.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Functional Characteristics of the E92K CFTR Gene Variant in the Russian and Turkish Population of People with Cystic Fibrosis

Kondratyeva

Melyanovskaya

Bulatenko

et al. 2023

IJMS

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The pathogenic variant E92K (c.274G > A) of the CFTR gene is rare in America and Europe, but it is common for people with cystic fibrosis from Russia and Turkey. We studied the effect of the E92K genetic variant on the CFTR function. The function of the CFTR channel was studied using the intestinal current measurements (ICM) method. The effects of CFTR modulators on the restoration of the CFTR function were studied in the model of intestinal organoids. To assess the effect of E92K on pre-mRNA splicing, the RT-PCR products obtained from patients’ intestinal organoid cultures were analyzed. Patients with the genetic variant E92K are characterized by an older age of diagnosis compared to homozygotes F508del and a high frequency of pancreatic sufficiency. The results of the sweat test and the ICM method showed partial preservation of the function of the CFTR channel. Functional analysis of CFTR gene expression revealed a weak effect of the E92K variant on mRNA-CFTR splicing. Lumacaftor (VX-809) has been shown to restore CFTR function in an intestinal organoid model, which allows us to consider the E92K variant as a promising target for therapy with CFTR correctors.

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Section: Discussionmentioning

confidence: 99%

Clinical and Functional Characteristics of the E92K CFTR Gene Variant in the Russian and Turkish Population of People with Cystic Fibrosis

Kondratyeva

Melyanovskaya

Bulatenko

et al. 2023

IJMS

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DNA copy number analysis of the DFNB1 hereditary hearing loss locus

2017

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Problems and achievements in the study of clinical and genetic aspects of cystic fibrosis

2022

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Cystic fibrosis is a common hereditary autosomal recessive disease characterized by pronounced genetic heterogeneity, associated clinical polymorphism, severe course and prognosis. The disease occurs worldwide in representatives of various populations and ethnic groups, with equal frequency among the male and female population. The molecular pathogenesis of the disease is based on disturbances in the synthesis, structure and function of the cystic fibrosis transmembrane conductance regulator protein (CFTR), which leads to various functional disorders in the work of chloride channels. As a result, the viscosity of secretions increases and exocrinopathy develops, which leads to disruption in the functioning of all organs and systems. The main cause of cystic fibrosis is a mutation in the CFTR gene. There are seven genetic classes of mutations in the CFTR gene, they mainly determine the severity of the disease. The main criterion in the diagnosis of cystic fibrosis is an increase in the concentration of chlorine ions in the secretion of sweat glandsof more than 60mmol/l when performing a sweat test using the classical GibsonCook method. An exception is a mutation in the CFTR 3849+10kbCT gene, which is associated with anormal or borderline sweat test result. For a long time, the treatment of patients suffering from cystic fibrosis was symptomatic, while the course of the disease remained severe and led to early mortality of patients. However, in recent decades, modern achievements in the field of studying the molecular genetic aspects of cystic fibrosis have made it possible to make a scientific breakthrough in the creation of pathogenetic therapy for this disease. New effective drugs that improve the health of patients and their quality of life have appeared. The relevance of studying the molecular mechanism of the disease for the development of a personalized approach in the treatment of cystic fibrosis is increasing, which is a promising direction on the way to gaining health for this category of patients.

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Features of cystic fibrosis in the Chuvash Republic

Cited by 3 publications

References 7 publications

Clinical and Functional Characteristics of the E92K CFTR Gene Variant in the Russian and Turkish Population of People with Cystic Fibrosis

Clinical and Functional Characteristics of the E92K CFTR Gene Variant in the Russian and Turkish Population of People with Cystic Fibrosis

DNA copy number analysis of the DFNB1 hereditary hearing loss locus

Problems and achievements in the study of clinical and genetic aspects of cystic fibrosis

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