310 Mira Street, Stavropol, Russia, 355017
+7 8652 352524; +7 8652 353229.
+7 8652 352524.
The journal is included into The list of leading scientific periodicals.
The article presents a clinical case of a patient with the genotype 2184insA/L138ins c.[2052dupA];[413_415dupTAC] and describes the course of the disease. The patient underwent intestinal current measurement (ICM) studies and a forskolin test on intestinal organoids using biopsy material of the rectum. The results of the study confirm the «mildness» of the genetic variant of L138ins, which is fully consistent with the clinical and functional assessment of pancreatic function: the absence of a picture of pancreatic insufficiency both in childhood and adulthood, with normal rates of fecal elastase. Although it was shown by the method of intestinal organoids that the genotype 2184insA/L138ins leads to a significant decrease in the functional activity of the CFTR protein, despite the presence of a pathogenic variant of class IV in the genotype.
1. Registry of Patients with Cystic Fibrosis in the Russian Federation. 2012. (In Russ.).
2. Registry of cystic fibrosis patients in Russian Federation. 2017. Edited by Voronkova A., Amelina E., Kashirskaya N., Kondratyeva E., Krasovsky S. [et al.] M.: Medpraktika-M, 2019. (In Russ).
3. Krasovsky S. A., Kashirskaya N. Yu., Chernyak A. V., Amelina E. L., Petrova N. V. [et al.]. Genetic characterization of cystic fibrosis patients in Russian Federation according to the National Register, 2014. Pulmonologiya. – Pulmonology. 2016;26(2):133-151. (In Russ). https://doi.org/10.18093/0869-0189-2016-26-2-133-151
4. Derichs N., Sanz J., Von Kanel T., Stolpe C., Zapf A. [et al.]. Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data. Thorax. 2009;65:594-599. https://doi.org/10.1136/thx.2009.125088
5. Clancy J. P., Szczesniak R. D., Ashlock M. A., Ernst S. E., Fan L. [et al.]. Multicenter Intestinal Current Measurements in Rectal Biopsies from CF and Non-CF Subjects to Monitor CFTR Function. Plos One J. 2013;8(9):e73905.
6. Boj S. F., Vonk A. M., Statia M. [et al.]. Forskolin-induced swelling in intestinal organoids: an in vitro assay for assessing drug response in cystic fibrosis patients. J. Vis. Exp. 2017;11(120). https://doi.org/10.3791/55159
7. Kondratyeva E. I., Melyanovskaya Yu. L., Efremova A. S., Bulatenko N. V., Bukharova T. B. [et al.]. Clinical and genetic and functional characteristics of patients with cystic fibrosis with the first described genetic variant CFTR c.1083G>A (p.Trp361X). Meditsinskaya genetika. – Medical genetics.2019;18.9(206):9-18. (In Russ.)
Keywords: сystic fibrosis, genetic variants, CFTR gene, intestinal current measurement, CFTR protein, intestinal organoids, forskolin test, corrector VX-809, potentiator VX-770