{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:03:17Z","timestamp":1791453797782,"version":"4.3.3"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["PEDEMO20G0"],"award-info":[{"award-number":["PEDEMO20G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["FFC #10\/2021"],"award-info":[{"award-number":["FFC #10\/2021"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italian Cystic Fibrosis Foundation","award":["PEDEMO20G0"],"award-info":[{"award-number":["PEDEMO20G0"]}]},{"name":"Italian Cystic Fibrosis Foundation","award":["FFC #10\/2021"],"award-info":[{"award-number":["FFC #10\/2021"]}]},{"name":"Italian Ministry of Health","award":["PEDEMO20G0"],"award-info":[{"award-number":["PEDEMO20G0"]}]},{"name":"Italian Ministry of Health","award":["FFC #10\/2021"],"award-info":[{"award-number":["FFC #10\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>S737F is a Cystic Fibrosis (CF) transmembrane conductance regulator (CFTR) missense variant. The aim of our study was to describe the clinical features of a cohort of individuals carrying this variant. In parallel, by exploiting ex vivo functional and molecular analyses on nasal epithelia derived from a subset of S737F carriers, we evaluated its functional impact on CFTR protein as well as its responsiveness to CFTR modulators. We retrospectively collected clinical data of all individuals bearing at least one S737F CFTR variant and followed at the CF Centre of Tuscany region (Italy). Nasal brushing was performed in cooperating individuals. At study end clinical data were available for 10 subjects (mean age: 14 years; range 1\u201344 years; 3 adult individuals). Five asymptomatic subjects had CF, 2 were CRMS\/CFSPID and 3 had an inconclusive diagnosis. Ex vivo analysis on nasal epithelia demonstrated different levels of CF activity. In particular, epithelia derived from asymptomatic CF subjects and from one of the subjects with inconclusive diagnosis showed reduced CFTR activity that could be rescued by treatment with CFTR modulators. On the contrary, in the epithelia derived from the other two individuals with an inconclusive diagnosis, the CFTR-mediated current was similar to that observed in epithelia derived from healthy donors. In vitro functional and biochemical analysis on S737F-CFTR expressed in immortalized bronchial cells highlighted a modest impairment of the channel activity, that was improved by treatment with ivacaftor alone or in combination with tezacaftor\/elexacaftor. Our study provide evidence towards the evaluation of CFTR function on ex vivo nasal epithelial cell models as a new assay to help clinicians to classify individuals, in presence of discordance between clinical picture, sweat test and genetic profile.<\/jats:p>","DOI":"10.3390\/ijms24076576","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T03:08:31Z","timestamp":1680491311000},"page":"6576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clinical Consequences and Functional Impact of the Rare S737F CFTR Variant and Its Responsiveness to CFTR Modulators"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1106-4424","authenticated-orcid":false,"given":"Vito","family":"Terlizzi","sequence":"first","affiliation":[{"name":"Department of Paediatric Medicine, Meyer Children\u2019s Hospital IRCCS, Cystic Fibrosis Regional Reference Center, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Pesce","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Capurro","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3761-1916","authenticated-orcid":false,"given":"Valeria","family":"Tomati","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariateresa","family":"Lena","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, 16126 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Pastorino","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8415-3802","authenticated-orcid":false,"given":"Renata","family":"Bocciardi","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, 16126 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Zara","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, 16126 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Centrone","sequence":"additional","affiliation":[{"name":"Diagnostic Genetics Unit, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9448-5381","authenticated-orcid":false,"given":"Giovanni","family":"Taccetti","sequence":"additional","affiliation":[{"name":"Department of Paediatric Medicine, Meyer Children\u2019s Hospital IRCCS, Cystic Fibrosis Regional Reference Center, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1916-0963","authenticated-orcid":false,"given":"Carlo","family":"Castellani","sequence":"additional","affiliation":[{"name":"UOSD Centro Fibrosi Cistica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5161-1720","authenticated-orcid":false,"given":"Nicoletta","family":"Pedemonte","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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. 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