{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:30:06Z","timestamp":1760146206112,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Cystic fibrosis (CF) is a multisystem disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We describe the distribution of CFTR mutation profiles in sub-tropical Queensland, Australia, and characterise the phenotypes associated with \u2018rare\u2019 CFTR mutation combinations. Methods: We conducted a retrospective observational study to analyse the CFTR mutation profiles of 322 people with CF (pwCF) under the care of a large adult CF centre in Queensland, Australia. Molecular pathology results were available for all identifiable CFTR mutations. The CFTR2 database was utilised to characterise the less common CFTR mutations to define mutation classes and explore associated phenotypic sequelae. Results: In total, eighty-seven different genotypes were identified within our CF cohort, with the most abundant mutation being the F508del mutation, 298\/322 (92.5%). Thirty-six pwCF with CFTR mutations are considered to have \u2018rare\u2019 CFTR mutations, and eleven with previously undefined phenotypes. For these eleven pwCF, late diagnosis in adulthood was confirmed in 5\/11 pwCF (45.5%) with CFTR modulator therapy only initiated in 5\/11 (45.5%). Conclusions: The profile of more common CFTR genotypes within our cohort of adult pwCF living in Queensland, Australia, generally reflects the global predominance of F508del, G542X, G551D, N1303K, and R117H. The phenotypic heterogeneity of disease seen within the eleven pwCF in our cohort with previously undefined CFTR genotypes highlights that rare mutations can also be associated with severe disease and continue to be at risk of delayed diagnosis. Access to CFTR modulator therapies for this group of pwCF remains limited and should remain a research priority.<\/jats:p>","DOI":"10.3390\/jcm13206210","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T06:46:52Z","timestamp":1729234012000},"page":"6210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenotypic Evaluation of Rare Cystic Fibrosis Transmembrane Conductance Regulator Mutation Combinations in People with Cystic Fibrosis in Queensland, Australia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9669-0805","authenticated-orcid":false,"given":"Ieuan Edward Shepherd","family":"Evans","sequence":"first","affiliation":[{"name":"Department of Thoracic Medicine, Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Brisbane, QLD 4032, Australia"},{"name":"Faculty of Medicine, University of Queensland, Brisbane, QLD 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine, Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Brisbane, QLD 4032, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine, Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Brisbane, QLD 4032, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9517-8212","authenticated-orcid":false,"given":"David William","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine, Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Brisbane, QLD 4032, Australia"},{"name":"Faculty of Medicine, University of Queensland, Brisbane, QLD 4006, Australia"},{"name":"Lung Inflammation & Infection, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1091\/mbc.e14-04-0935","article-title":"From CFTR biology toward combinatorial pharmacotherapy: Expanded classification of cystic fibrosis mutations","volume":"27","author":"Veit","year":"2016","journal-title":"Mol. 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