{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T04:34:16Z","timestamp":1775363656838,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T00:00:00Z","timestamp":1749859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: One of the most common genetic variants among individuals with cystic fibrosis screen-positive inconclusive diagnosis (CFSPID) is 5T;12TG. Classified as having \u201cvarying clinical consequences\u201d (VVCC), it may produce a wide spectrum of CF phenotypes when combined in trans with a pathogenic variant on the other CFTR allele, ranging from asymptomatic cases to CFTR-related disorders (CFTR-RD) or classical cystic fibrosis (CF). The 5T;12TG variant is currently eligible for modulator treatment in the United States. Methods: We conducted a retrospective analysis of CFSPID children born between July 2009 and June 2023 in the Community of Madrid (Spain) who carried at least one 5T;12TG variant in trans with another CFTR variant. Data collected included trends in sweat chloride (SC) values, respiratory and digestive symptoms, lung function by spirometry, microbiological findings in nasopharyngeal aspirates, anthropometric data, and fecal elastase levels. Results: Twenty-one children (52.3% females; median age: 4.66 years [IQR 3.6\u20136.9]) were included. Eighteen had 5T;12TG in trans with a CF-causing variant (CFc), two had another VVCC variant, and one had a variant of unknown significance (VUS). After a median follow-up of 3.45 years [IQR 1.4\u20134.3], all the children remained asymptomatic. However, SC values rose to intermediate levels in nine (42.8%) of the children. No isolates of Pseudomonas aeruginosa were identified. Lung function and pancreatic markers remained normal. Conclusions: This is the first Spanish cohort of children with CFSPID and the 5T;12TG allele. Although clinical symptoms did not manifest during childhood, the SC value increased to intermediate values in 42.8% of the cohort, so these may require long-term follow-up to observe conversions to CFTR-RD or CF. The potential initiation of modulator therapy based solely on SC levels or emerging symptoms warrants careful consideration.<\/jats:p>","DOI":"10.3390\/children12060778","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T14:03:11Z","timestamp":1750082591000},"page":"778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Significance of the 5T;12TG Genotype in Pediatric CFSPID: A Retrospective Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Ana","family":"Morales-Tirado","sequence":"first","affiliation":[{"name":"Cystic Fibrosis Unit, Department of Pediatric Medicine, Ramon y Cajal University Hospital, M-607, Km. 9, 100, Fuencarral-El Pardo, 28034 Madrid, Spain"},{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (Irycis), M-607, Km. 9, 100, Fuencarral-El Pardo, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique","family":"Blitz-Castro","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Unit, Department of Pediatric Medicine, Ramon y Cajal University Hospital, M-607, Km. 9, 100, Fuencarral-El Pardo, 28034 Madrid, Spain"},{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (Irycis), M-607, Km. 9, 100, Fuencarral-El Pardo, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saioa","family":"Vicente-Santamar\u00eda","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Unit, Department of Pediatric Medicine, Ramon y Cajal University Hospital, M-607, Km. 9, 100, Fuencarral-El Pardo, 28034 Madrid, Spain"},{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (Irycis), M-607, Km. 9, 100, Fuencarral-El Pardo, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Luna-Paredes","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Unit, Department of Pediatric Medicine, Doce de Octubre University Hospital, Av. de C\u00f3rdoba, s\/n, Usera, 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0668-3506","authenticated-orcid":false,"given":"Enrique","family":"Salcedo-Lobato","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Unit, Department of Pediatric Medicine, Doce de Octubre University Hospital, Av. de C\u00f3rdoba, s\/n, Usera, 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Tabares-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Unit, Department of Pediatric Medicine, Ramon y Cajal University Hospital, M-607, Km. 9, 100, Fuencarral-El Pardo, 28034 Madrid, Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (Irycis), M-607, Km. 9, 100, Fuencarral-El Pardo, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia","family":"Gasc\u00f3n-Galindo","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Unit, Department of Pediatric Medicine, Ramon y Cajal University Hospital, M-607, Km. 9, 100, Fuencarral-El Pardo, 28034 Madrid, Spain"},{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (Irycis), M-607, Km. 9, 100, Fuencarral-El Pardo, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Boutry","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne, Station 1, 1015 Lausanne, Switzerland"},{"name":"Swiss Institute of Bioinformatics, Station 1, 1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adelaida","family":"Lamas-Ferreiro","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Unit, Department of Pediatric Medicine, Ramon y Cajal University Hospital, M-607, Km. 9, 100, Fuencarral-El Pardo, 28034 Madrid, Spain"},{"name":"Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (Irycis), M-607, Km. 9, 100, Fuencarral-El Pardo, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S2213-2600(19)30337-6","article-title":"The Lancet Respiratory Medicine Commission on the Future of Care of Cystic Fibrosis","volume":"8","author":"Bell","year":"2020","journal-title":"Lancet Respir. 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Fibros."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/6\/778\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:52:12Z","timestamp":1760032332000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/6\/778"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,14]]},"references-count":32,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["children12060778"],"URL":"https:\/\/doi.org\/10.3390\/children12060778","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,14]]}}}