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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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Detalles Bibliográficos
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
Descripción
Sumario: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.