{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T22:15:02Z","timestamp":1764540902013,"version":"3.46.0"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"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>Background<\/jats:title>\n                    <jats:p>Cystic Fibrosis (CF) is primarily diagnosed in Germany through newborn screening (NS) using immunoreactive trypsinogen (IRT)\/Pancreatitis-Associated Protein (PAP) measurements and genetic testing for common CFTR gene variants. While this method is effective in identifying the most frequent mutations, it may overlook complex alleles, which can impact phenotype and treatment efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Presentation<\/jats:title>\n                    <jats:p>We report the case of a five-year-old girl diagnosed with CF through NS, initially identified as homozygous for the F508del variant. Despite early Orkambi therapy, her response was suboptimal, with high sweat chloride levels and recurrent respiratory infections. Re-sequencing with a next-generation sequencing (NGS) panel revealed an additional undetected heterozygous pathogenic variant. Upon switching to elexacaftor\/tezacaftor\/ivacaftor (ETI), sweat chloride levels significantly improved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Standard genetic screening methods may fail to detect complex alleles, leading to misinterpretation of genotype and suboptimal treatment choices. This case highlights the necessity of comprehensive genetic analysis in patients with unexpected therapy responses. When CFTR modulator therapy does not yield the expected improvements, re-sequencing should be considered to optimize precision medicine approaches for CF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2025.1693573","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T22:10:12Z","timestamp":1764540612000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Pitfalls in CF screening \u2013 targeted variant analysis can cause misleading results and therapy recommendations"],"prefix":"10.3389","volume":"16","author":[{"given":"Maike","family":"Karnstedt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Ahting","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Behrendt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maike vom","family":"Hove","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Hentschel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.jcf.2023.10.009","article-title":"Every CFTR variant counts - target-capture based next-generation-sequencing for molecular diagnosis in the German cf registry","volume":"23","author":"Ahting","year":"2024","journal-title":"J. Cystic Fibrosis Official Journal Eur. Cyst. Fibros. Soc."},{"key":"B2","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S2213-2600(19)30337-6","article-title":"The future of cystic fibrosis care: a global perspective","volume":"8","author":"Bell","year":"2020","journal-title":"Lancet. Respir. Medicine"},{"key":"B3","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/S2213-2600(16)00023-0","article-title":"Progress in therapies for cystic fibrosis","volume":"4","author":"Boeck","year":"2016","journal-title":"Lancet. Respir. Medicine"},{"key":"B4","doi-asserted-by":"publisher","first-page":"S15","DOI":"10.1016\/j.jcf.2019.12.008","article-title":"The influence of CFTR complex alleles on precision therapy of cystic fibrosis","volume":"19","author":"Chevalier","year":"2020","journal-title":"J. Cystic Fibrosis Official Journal Eur. Cyst. Fibros. 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Fetal Neonatal Med."},{"key":"B13","article-title":"German cystic fibrosis registry annual report 2023","author":"N\u00e4hrlich","year":"2023"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.3390\/genes14081608","article-title":"Next-generation sequencing for screening analysis of cystic fibrosis: spectrum and novel variants in a south-central Italian cohort","volume":"14","author":"Paolis","year":"2023","journal-title":"Genes"},{"key":"B15","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Medicine Official Journal Am. Coll. Med. 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