Selection of CFTR modulators for children with the W1282R variant

Objective. To study the clinical manifestations of W1282R variant, functional activity cystic fibrosis transmembrane conductance regulator (CFTR) channel, and effectiveness CFTR modulator therapy in patients with variant. Materials methods included medical records, intestinal current measurement method (ICM) organoids (IO). Results. The c.3844T>C (p.Trp1282Arg, W1282R) variant refers to missense mutations. Cystic Fibrosis (CF) Patient Registry Russian Federation (2019) provides data on 34 genotype. Clinical two corresponds severe course CF. ICM revealed loss function. effect VX-809 corrector, VX-770 potentiator their combined use were assessed each patient using IO. Conclusion. results indicated a “severe” application corrector had no restoration chloride channel function, unlike F508del homozygous control sample (class II mutations). kinetic properties protein. But both patients, significant lost function (~45%) was recorded potentiator, which is typical for class III IV variants. This challenges conclusions that has characteristics only. Combination may be recommended W1282R/CFTRdel2,3 W1282R/F508del genotypes. Key words: fibrosis, gene, pathogenic method, organoids, forskolin-induced swelling assay, correctors, potentiators, target therapy, ivacaftor, lumacaftor