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3 results on '"Nataliya Bulatenko"'

1. Personalized Selection of a CFTR Modulator for a Patient with a Complex Allele [L467F;F508del]

Author

Elena Kondratyeva, Nataliya Bulatenko, Yuliya Melyanovskaya, Anna Efremova, Elena Zhekaite, Viktoriya Sherman, Anna Voronkova, Irina Asherova, Alexander Polyakov, Tagui Adyan, Valeriia Kovalskaia, Tatiana Bukharova, Dmitry Goldshtein, and Sergey Kutsev

Subjects
cystic fibrosis (CF), complex allele, targeted therapy, intestinal current measurements (ICM), intestinal organoids, CFTR modulators, Biology (General), QH301-705.5
Abstract

The presence of complex alleles in the CFTR gene can lead to difficulties in diagnosing cystic fibrosis and cause resistance to therapy with CFTR modulators. Tezacaftor/ivacaftor therapy for 8 months in a patient with the initially established F508del/F508del genotype did not lead to an improvement in her condition—there was no change in spirometry and an increase in the patient’s weight, while there was only a slight decrease in NaCl values, measured by a sweat test. The intestinal current measurements of the patient’s rectal biopsy showed no positive dynamics in the rescue of CFTR function while taking tezacaftor/ivacaftor. The assumption that the patient had an additional mutation in the cis position was confirmed by sequencing the CFTR gene, and the complex allele [L467F;F508del] was identified. Based on the rescue of CFTR function by elexacaftor/tezacaftor/ivacaftor obtained using forskolin-induced swelling on intestinal organoids, the patient was prescribed therapy with this targeted drug. The use of elexacaftor/tezacaftor/ivacaftor for 7 months resulted in a significant improvement in the patient’s clinical condition.

Published
2022
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2. Evaluation of the Complex p.[Leu467Phe;Phe508del] CFTR Allele in the Intestinal Organoids Model: Implications for Therapy

Author

Elena Kondratyeva, Anna Efremova, Yuliya Melyanovskaya, Anna Voronkova, Alexander Polyakov, Nataliya Bulatenko, Tagui Adyan, Viktoriya Sherman, Valeriia Kovalskaia, Nika Petrova, Marina Starinova, Tatiana Bukharova, Sergei Kutsev, and Dmitry Goldshtein

Subjects
Cystic Fibrosis, Colforsin, Organic Chemistry, Cystic Fibrosis Transmembrane Conductance Regulator, General Medicine, Catalysis, Computer Science Applications, Ligases, Organoids, Inorganic Chemistry, cystic fibrosis (CF), CFTR, complex allele [L467F, F508del], intestinal current measurements (ICM), intestinal organoids, CFTR modulators, Mutation, Humans, Benzodioxoles, Physical and Theoretical Chemistry, Molecular Biology, Alleles, Spectroscopy
Abstract

In the cohort of Russian patients with cystic fibrosis, the p.[Leu467Phe;Phe508del] complex allele (legacy name [L467F;F508del]) of the CFTR gene is understudied. In this research, we present the results of frequency evaluation of the [L467F;F508del] complex allele in the Russian Federation among patients with a F508del/F508del genotype, its effect on the clinical course of cystic fibrosis, the intestinal epithelium ionic channel function, and the effectiveness of target therapy. The frequency of the [L467F;F508del] complex allele among patients with homozygous F508del was determined with multiplex ligase-dependent probe amplification followed by polymerase chain reaction and fragment analysis. The function of ionic channels, including the residual CFTR function, and the effectiveness of CFTR modulators was analyzed using intestinal current measurements on rectal biopsy samples and the forskolin-induced swelling assay on organoids. The results showed that the F508del/[L467F;F508del] genotype is present in 8.2% of all Russian patients with F508del in a homozygous state. The clinical course of the disease in patients with the F508del/[L467F;F508del] genotype is severe and does not vary from the course in the cohort with homozygous F508del, although the CFTR channel function is significantly lower. For patients with the F508del/[L467F;F508del] genotype, we can recommend targeted therapy using a combined ivacaftor + tezacaftor + elexacaftor medication.

Published
2022
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3. Clinical and Functional Characteristics of the E92K CFTR Gene Variant in the Russian and Turkish Population of People with Cystic Fibrosis

Author

Elena Kondratyeva, Yuliya Melyanovskaya, Nataliya Bulatenko, Ksenia Davydenko, Alexandra Filatova, Anna Efremova, Mikhail Skoblov, Tatiana Bukharova, Viktoriya Sherman, Anna Voronkova, Elena Zhekaite, Stanislav Krasovskiy, Elena Amelina, Nika Petrova, Alexander Polyakov, Tagui Adyan, Marina Starinova, Maria Krasnova, Andrey Vasilyev, Oleg Makhnach, Rena Zinchenko, Sergey Kutsev, Yasemin Gokdemir, Bülent Karadag, Dmitry Goldshtein, and Kondratyeva E., Melyanovskaya Y., Bulatenko N., Davydenko K., Filatova A., Efremova A., Skoblov M., Bukharova T., Sherman V., Voronkova A., et al.

Subjects
Temel Bilimler (SCI), Mühendislik, ENGINEERING, Biochemistry, Physical Chemistry, Organik Kimya, Kimya, KİMYA, İNORGANİK VE NÜKLEER, CHEMISTRY, Biyokimya, Kimya Mühendisliği ve Teknolojisi, MÜHENDİSLİK, KİMYASAL, CHEMISTRY, INORGANIC & NUCLEAR, CFTR, intestinal current measurements (ICM), Spectroscopy, Bilgisayar Bilimi Uygulamaları, Computer Sciences, Moleküler Biyoloji, Temel Bilimler, Spektroskopi, KİMYA, FİZİKSEL, Fizikokimya, Life Sciences, CHEMISTRY, ORGANIC, Kataliz, genotype–phenotype correlation, General Medicine, Computer Science Applications, MOLECULAR BIOLOGY & GENETICS, Natural Sciences (SCI), Physical Sciences, Engineering and Technology, Bilgisayar Bilimi, Natural Sciences, cystic fibrosis (CF), İnorganik kimya, CHEMISTRY, PHYSICAL, E92K, Life Sciences (LIFE), Fiziksel ve Teorik Kimya, Molecular Biology and Genetics, Chemical Engineering and Technology, Catalysis, Inorganic Chemistry, SPEKTROSKOPİ, VX-809 corrector, KİMYA, ORGANİK, Yaşam Bilimleri, Bilgisayar Bilimleri, Biyoinorganik Kimya, Physical and Theoretical Chemistry, Engineering, Computing & Technology (ENG), Bioinorganic Chemistry, Molecular Biology, Moleküler Biyoloji ve Genetik, VX-770 potentiator, Organic Chemistry, Mühendislik, Bilişim ve Teknoloji (ENG), COMPUTER SCIENCE, Fizik Bilimleri, Yaşam Bilimleri (LIFE), intestinal organoids, CF Registry, forskolin-induced swelling (FIS) assay, Mühendislik ve Teknoloji, ENGINEERING, CHEMICAL
Abstract

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.

Published
2023
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