Functional activity of the CFTR channel in a patient with the [L467F;F508del]/W1310X genotype-Reference-Cited by-同舟云学术

Functional activity of the CFTR channel in a patient with the [L467F;F508del]/W1310X genotype

Published:2024-03-15 Issue:2 Volume:34 Page:264-270
ISSN:2541-9617
Container-title:PULMONOLOGIYA
language:
Short-container-title:Pulʹmonologiâ (Mosk.)

Author:

Krasnova M. G.¹^ORCID,Mokrousova D. O.¹^ORCID,Efremova A. S.¹^ORCID,Melyanovskaya Yu. L.²^ORCID,Sherman V. D.¹^ORCID,Bukharova T. B.¹^ORCID,Goldshtein D. V.¹^ORCID

Affiliation:

1. Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation

2. Federal State Budgetary Scientific Institution “Research Centre for Medical Genetics”, Ministry of Science and Higher Education of the Russian Federation; State Budgetary Healthcare Institution of the Moscow region “Research Clinical Institute of Childhood”, Healthcare Ministry of Moscow Region

Abstract

An important factor influencing the severity of cystic fibrosis (CF) and the effectiveness of treatment is the presence of complex alleles in the CFTR gene ≥ 2 variants in one allele. The influence of such alleles on the manifestations of CF has not been sufficiently studied.The aim of this study was to investigate the effect of the complex allele [L467F;F508del] on the phenotypic manifestations of CF and the efficacy of targeted therapy in an intestinal organoid (IO) model in a patient with the [L467F;F508del]/W1310X genotype.Methods. Methods for determining the difference in intestinal potentials (IDP), the KO method, and the forskolin test are presented using the medical history of a patient with the [L467F;F508del]/ W1310X genotype as an example.Results. The patient was diagnosed with progressive disease with obvious deterioration of pulmonary function. The ORKP method showed the absence of chlorine channel function. An assay with a KO culture from intestinal tissue showed a complete loss of functional activity of the chloride channel. In addition, the complex allele [L467F;F508del] is not sensitive to the effect of all tested CFTR modulators.Conclusion. The complex allele [L467F;F508del] causes a complete loss of functional CFTR protein and is not sensitive to the effect of any of the registered targeted drugs.

Publisher

Scientific and Practical Reviewed Journal Pulmonology

Reference11 articles.

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