Study of CFTR channel functional activity in a patient with cystic fibrosis and E92K/4428insGA genotype

Abstract

Clinical manifestations of cystic fibrosis depend on the patient’s genotype since there are more than 2,000 variants of the CFTR gene. Main complications of the disease are expressed in a reduction or loss of pancreatic function and bacterial lung infection, leading to respiratory failure. The E92K (p.(Glu92Lys) and 4428insGA (p.(Ser1435Glyfs*14) mutations in the CFTR gene are accompanied by a high frequency of preserved pancreatic function. In a 3-year-old patient with recurrent pancreatitis and E92K/4428insGA genotype, the functional activity of the CFTR channel was studied using the intestinal current measurement method on rectal biopsy specimens and the forskolin-induced swelling assay in intestinal organoids. The personalized assessment of the action of CFTR modulators was also performed on organoid cultures obtained from the patient’s intestinal biopsies. In a 3-year-old child with cystic fibrosis and recurrent pancreatitis with frequent exacerbations, a high preservation of residual CFTR channel function was revealed. All the investigated targeted drugs were effective in increasing the functional activity of the CFTR chloride channel. Key words: cystic fibrosis, CFTR gene, targeted therapy, pancreatitis, intestinal organoids, intestinal current measurement, E92K, 4428insGA