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

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...

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Autores principales: Kondratyeva, Elena, Bulatenko, Nataliya, Melyanovskaya, Yuliya, Efremova, Anna, Zhekaite, Elena, Sherman, Viktoriya, Voronkova, Anna, Asherova, Irina, Polyakov, Alexander, Adyan, Tagui, Kovalskaia, Valeriia, Bukharova, Tatiana, Goldshtein, Dmitry, Kutsev, Sergey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600521/
https://www.ncbi.nlm.nih.gov/pubmed/36286063
http://dx.doi.org/10.3390/cimb44100349
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author Kondratyeva, Elena
Bulatenko, Nataliya
Melyanovskaya, Yuliya
Efremova, Anna
Zhekaite, Elena
Sherman, Viktoriya
Voronkova, Anna
Asherova, Irina
Polyakov, Alexander
Adyan, Tagui
Kovalskaia, Valeriia
Bukharova, Tatiana
Goldshtein, Dmitry
Kutsev, Sergey
author_facet Kondratyeva, Elena
Bulatenko, Nataliya
Melyanovskaya, Yuliya
Efremova, Anna
Zhekaite, Elena
Sherman, Viktoriya
Voronkova, Anna
Asherova, Irina
Polyakov, Alexander
Adyan, Tagui
Kovalskaia, Valeriia
Bukharova, Tatiana
Goldshtein, Dmitry
Kutsev, Sergey
author_sort Kondratyeva, Elena
collection PubMed
description 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.
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spelling pubmed-96005212022-10-27 Personalized Selection of a CFTR Modulator for a Patient with a Complex Allele [L467F;F508del] Kondratyeva, Elena Bulatenko, Nataliya Melyanovskaya, Yuliya Efremova, Anna Zhekaite, Elena Sherman, Viktoriya Voronkova, Anna Asherova, Irina Polyakov, Alexander Adyan, Tagui Kovalskaia, Valeriia Bukharova, Tatiana Goldshtein, Dmitry Kutsev, Sergey Curr Issues Mol Biol Article 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. MDPI 2022-10-21 /pmc/articles/PMC9600521/ /pubmed/36286063 http://dx.doi.org/10.3390/cimb44100349 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kondratyeva, Elena
Bulatenko, Nataliya
Melyanovskaya, Yuliya
Efremova, Anna
Zhekaite, Elena
Sherman, Viktoriya
Voronkova, Anna
Asherova, Irina
Polyakov, Alexander
Adyan, Tagui
Kovalskaia, Valeriia
Bukharova, Tatiana
Goldshtein, Dmitry
Kutsev, Sergey
Personalized Selection of a CFTR Modulator for a Patient with a Complex Allele [L467F;F508del]
title Personalized Selection of a CFTR Modulator for a Patient with a Complex Allele [L467F;F508del]
title_full Personalized Selection of a CFTR Modulator for a Patient with a Complex Allele [L467F;F508del]
title_fullStr Personalized Selection of a CFTR Modulator for a Patient with a Complex Allele [L467F;F508del]
title_full_unstemmed Personalized Selection of a CFTR Modulator for a Patient with a Complex Allele [L467F;F508del]
title_short Personalized Selection of a CFTR Modulator for a Patient with a Complex Allele [L467F;F508del]
title_sort personalized selection of a cftr modulator for a patient with a complex allele [l467f;f508del]
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600521/
https://www.ncbi.nlm.nih.gov/pubmed/36286063
http://dx.doi.org/10.3390/cimb44100349
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