{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T10:14:26Z","timestamp":1774347266717,"version":"3.50.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Cystic fibrosis (CF) is an autosomal recessive disease resulting from pathogenic CF transmembrane conductance regulator (\n                      <jats:italic>CFTR<\/jats:italic>\n                      ) pathogenic gene variants. While CF\u2019s 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\n                      <jats:italic>CFTR<\/jats:italic>\n                      using Oxford Nanopore Technology (ONT)-based long-read sequencing enhances the diagnostic yield.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      To amplify \u223c25-kb fragments covering the whole\n                      <jats:italic>CFTR<\/jats:italic>\n                      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&amp;gt;G p.Leu227Arg, c.1521_1523del p.Phe508del, c.3484C&amp;gt;T p.Arg1162*, c.1090T&amp;gt;C p.Ser364Pro, c.3233T&amp;gt;C p.Phe1078Ser and c.2991G&amp;gt;C p.Leu997Phe. The analytical pipeline we developed allowed the phasing of the variants. Sanger sequencing confirmed all these results. The previously uncharacterised\n                      <jats:italic>CFTR<\/jats:italic>\n                      variants p.Ser364Pro and p.Phe1078Ser exhibit diminished expression in HEK293 cells, substantiating their pathogenic nature, with p.Phe1078Ser responding positively to the\n                      <jats:italic>in vitro<\/jats:italic>\n                      treatment with CFTR-modulator molecules.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1769093","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T06:33:03Z","timestamp":1774333983000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CFTR gene variant detection in moroccan individuals via nanopore long-read sequencing"],"prefix":"10.3389","volume":"17","author":[{"given":"Nada","family":"El Makhzen","sequence":"first","affiliation":[{"name":"Ion Channels and Channelopathies Laboratory, Department of Medicine, Institute for Biochemistry and Molecular Medicine, University of Bern","place":["Bern, Switzerland"]},{"name":"Department of Medicine, Graduate School for Cellular and Biomedical Sciences, University of Bern","place":["Bern, Switzerland"]},{"name":"Department of research and innovation, Initiative Afrique of the University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Nater","sequence":"additional","affiliation":[{"name":"Department of Biology, Interfaculty Bioinformatics Unit (IBU) and Swiss Institute of Bioinformatics (SIB), University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-S\u00e9bastien","family":"Rougier","sequence":"additional","affiliation":[{"name":"Ion Channels and Channelopathies Laboratory, Department of Medicine, Institute for Biochemistry and Molecular Medicine, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Bokhobza","sequence":"additional","affiliation":[{"name":"Cardiac Calcium Regulation and Nanosignalling Group, Department of Physiology, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Sanz","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Zweier","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Flore","family":"H\u00e4mmerli","sequence":"additional","affiliation":[{"name":"Ion Channels and Channelopathies Laboratory, Department of Medicine, Institute for Biochemistry and Molecular Medicine, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9my","family":"Bruggmann","sequence":"additional","affiliation":[{"name":"Department of Biology, Interfaculty Bioinformatics Unit (IBU) and Swiss Institute of Bioinformatics (SIB), University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laila","family":"Bouguenouch","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Oncogenetics, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University","place":["Fez, Morocco"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mounia","family":"Lakhdar Idrissi","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Hassan II University Hospital","place":["Fez, Morocco"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugues","family":"Abriel","sequence":"additional","affiliation":[{"name":"Ion Channels and Channelopathies Laboratory, Department of Medicine, Institute for Biochemistry and Molecular Medicine, University of Bern","place":["Bern, Switzerland"]},{"name":"Department of research and innovation, Initiative Afrique of the University of Bern","place":["Bern, Switzerland"]},{"name":"Cluster of Research Excellence Genomics for Health in Africa, University of Bern","place":["Bern, Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"B2","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1002\/humu.10041","article-title":"Cystic fibrosis: a worldwide analysis of CFTR mutations\u2014correlation with incidence data and application to screening","volume":"19","author":"Bobadilla","year":"2002","journal-title":"Hum. 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