Study of a rare variant of the CFTR c.1329_1350del gene in a homozygous state in a child with cystic fibrosis using functional tests

   The study of rare variants in the CFTR gene is relevant in the era of targeted therapy with CFTR modulators. In this study, we studied the clinical picture of cystic fibrosis, as well as the function of the CFTR channel in a homozygous carrier of a rare pathogenic variant c.1329_1350del (p.Asp443GlufsX19), belonging to class I disorders in the CFTR gene. A complete correlation of the results of functional tests with the phenotypic pattern of CF and data of a sweat test was obtained. The method for determining the difference in intestinal potentials demonstrated the absence of functional activity of the chloride CFTR channel in the rectal biopsy, and when stimulated with forskolin, the patient’s organoids did not swell, which indicates a complete violation of the functional CFTR protein production. Exposure to intestinal organoids by all registered for therapy targeted drugs did not lead to their swelling, unlike the control culture, homozygous for F508del. The chloride channel of a patient with genotype p.Asp443GlufsX19/p.Asp443GlufsX19 turned out to be insensitive to any CFTR modulator.

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