Genetic and Functional Characteristics of Pathogenic Variant E92K of CFTR Gene Among Cystic Fibrosis Patients in the Russian and Turkish Populations Were Studied

Employees of the scientific clinical department for cystic fibrosis, stem cell genetics laboratory, laboratory of genetic epidemiology and laboratory of functional genomics of the Research Centre for Medical Genetics, together with Turkish colleagues, have studied the genetic and functional characteristics of the pathogenic variant E92K of the CFTR gene in patients with cystic fibrosis in the Russian and Turkish populations.

According to the National Cystic Fibrosis Register, the variant E92K (c.274G>A) is one of the three most common (3.25%) and widely distributed among the Turkic-speaking population of Volgo-Ural region with a maximum frequency among the Chuvash population (55%) in the Russian Federation. According to the National Register of Cystic Fibrosis Patients in Turkey for 2020, the E92K frequency is 2.7%.

The CFTR channel function was studied by intestinal potentials differentiation, which showed partial retention of channel function in patients with this pathogenic variant. The influence of CFTR modulators on CFTR channel recovery has been studied on intestinal organoids. Lumacaftor (VX-809) drug has been shown to restore CFTR function, making E92K a promising target for corrective therapy. In addition, researchers have assessed the impact of E92K on splicing pre-mRNA. Functional analysis of CFTR gene expression revealed a weak influence of E92K on mRNA-CFTR splicing.

The results of the research were published in the report «Clinical and Functional Characteristics of the E92K CFTR Gene Variant in the Russian and Turkish Population of People with Cystic Fibrosis».

More information about the materials of the article can be found at: https://doi.org/10.3390/ijms24076351 E.I. Kondratieva, Yu.L. Melyanovskaya, N.V. Bulatenko, K.A. Dadevenko, A.Y. Buhkova,  A.S. Yef., REM.M., Kirova,  V.V.B. Kirova, .V.V. Kirova, .V. Kirova, Kirova,  V.V.E.R. S.A. Krasovskiy, E.L. Amelina, N.V. Petrova, A.V. Polyakov, T.A. Adyan, M.A. Starkova, M. Krasnova, A.V. Vasilyev, O.V. Makhnach, R.A. Zinchenko, S. Kudmitry, V.K. Clinical and Functional Characteristics of the E92K CFTR Gene Variant in the Russian and Turkish Population of People with Cystic Fibrosis. Int. J. Mol. Sci. 2023, 24, 6351.