ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
CFTR Gene Variant Detection in Moroccan Individuals via Nanopore Long-Read Sequencing
Nada EL Makhzen 1
Alexander Nater 2
Jean-Sébastien Rougier 1
Alexandre Bokhobza 2
Javier Sanz 3
Christiane Zweier 3
Anne-Flore Hämmerli 1
Rémy Bruggmann 2
Laila Bouguenouch 4
Mounia Lakhdar Idrissi 4
Hugues Abriel 1
1. Institute of Biochemistry and Molecular Medicine, Department of Preclinical Medicine, Faculty of Medicine, University of Bern, Bern, Switzerland
2. Universitat Bern, Bern, Switzerland
3. Inselspital Universitatsspital Bern, Bern, Switzerland
4. Universite Sidi Mohamed Ben Abdellah, Fes, Morocco
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Abstract
Introduction: Cystic fibrosis (CF) is an autosomal recessive disease resulting from pathogenic CF transmembrane conductance regulator (CFTR) pathogenic gene variants. While CF's frequency varies among ethnicities, its epidemiology, clinical manifestations, and mutational profiles in Africa still must be explored due to the absence of a comprehensive public health strategy there. This study postulates that complete sequencing of CFTR using Oxford Nanopore Technology (ONT)-based long-read sequencing enhances the diagnostic yield. Methods and Results: To amplify ~25-kb fragments covering the whole CFTR gene (NM_000492.4), we designed 11 primer pairs, and barcoded libraries were prepared and sequenced on ONT flow cells (R10.4.1) using an Mk1C device. Variant pathogenicity was assessed by expressing the variant channel in HEK293 cells and examining expression through immuno-blotting. With sequencing data obtained from 9 Moroccan individuals (6 probands with suspected CF diagnoses and 3 parents), we identified the following variants: c.680T>G p.Leu227Arg, c.1521_1523del p.Phe508del, c.3484C>T p.Arg1162*, c.1090T>C p.Ser364Pro, c.3233T>C p.Phe1078Ser and c.2991G>C p.Leu997Phe. The analytical pipeline we developed allowed the phasing of the variants. Sanger sequencing confirmed all these results. The previously uncharacterised CFTR variants p.Ser364Pro and p.Phe1078Ser exhibit diminished expression in HEK293 cells, substantiating their pathogenic nature, with p.Phe1078Ser responding positively to the in vitro treatment with CFTR-modulator molecules. Conclusion: This study demonstrates the potential of long-read sequencing using ONT as an efficient means to detect CF-causing variants in African populations. Given the significant genetic heterogeneity in Africa, this technique can serve as an affordable molecular screening tool for CF, especially in areas with constrained access to genetic screening.
Summary
Keywords
CF transmembrane conductance regulator, CFTR, Cystic Fibrosis, Long-read sequencing, Oxford Nanopore Technology
Received
16 December 2025
Accepted
18 February 2026
Copyright
© 2026 EL Makhzen, Nater, Rougier, Bokhobza, Sanz, Zweier, Hämmerli, Bruggmann, Bouguenouch, Lakhdar Idrissi and Abriel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Nada EL Makhzen
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