{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:12:19Z","timestamp":1776852739393,"version":"3.51.2"},"reference-count":60,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Previous studies reported the influence of cis variants in F508del cystic fibrosis (CF) patients in their responses to CFTR modulators. The current study is a prospective, observational study involving three patients with CF and pancreatic insufficiency, carrying a complex allele including F508del with A238V, I1027T, or L467F. We report clinical data before and after 4 weeks of treatment with tezacaftor (TEZ)\/ivacaftor (IVA), elexacaftor (ELX)\/TEZ\/IVA, and lumacaftor (LUM)\/IVA for patients with complex alleles A238V, I1027T, and L467F, respectively. The 50-year-old patient bearing F508del;A238V\/D1152H showed a normal sweat test (13 mEq\/L) and improvements in forced expiratory volume in the first second (FEV1) (+7 points), body mass index (BMI) (+0.85), and respiratory CF Questionnaire-Revised (CFQ-R) domain (+22.2 points). The 12-year-old patient bearing F508del;I1027T\/R709X showed an improvement in a sweat test (\u221240 mEq\/l), FEV1 (+9 points) and the respiratory CFQ-R domain (+16.7 points). No changes in outcomes were observed for the 6-year-old patient F508del;L467F\/F508del. Our data highlight that the reported variants do not modify the phenotypic expression of F508del. Searching L467F is crucial in CF patients with F508del nonresponsive to ELX\/TEZ\/IVA. Further data are needed to evaluate the clinical effect of these variants after a longer follow up.<\/jats:p>","DOI":"10.3390\/jpm12091421","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T01:50:51Z","timestamp":1661997051000},"page":"1421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Modulator Therapy in Cystic Fibrosis Patients with cis Variants in F508del Complex Allele: A Short-Term Observational Case Series"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1106-4424","authenticated-orcid":false,"given":"Vito","family":"Terlizzi","sequence":"first","affiliation":[{"name":"Department of Paediatric Medicine, Cystic Fibrosis Regional Reference Center, Meyer Children\u2019s Hospital, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Centrone","sequence":"additional","affiliation":[{"name":"Diagnostic Genetics Unit, Careggi University Hospital, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, Meyer Children\u2019s Hospital, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Castellani","sequence":"additional","affiliation":[{"name":"Department of Radiology, Meyer Children\u2019s Hospital, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7714-8095","authenticated-orcid":false,"given":"Tarini N. A.","family":"Gunawardena","sequence":"additional","affiliation":[{"name":"Programme in Molecular Medicine, The Hospital for Sick Children, Toronto, ON M5G 8X4, Canada"},{"name":"Programme in Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 8X4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Taccetti","sequence":"additional","affiliation":[{"name":"Department of Paediatric Medicine, Cystic Fibrosis Regional Reference Center, Meyer Children\u2019s Hospital, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0237-4079","authenticated-orcid":false,"given":"Onofrio","family":"Laselva","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/S0140-6736(20)32542-3","article-title":"Cystic fibrosis","volume":"397","author":"Shteinberg","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200016","DOI":"10.1183\/20734735.0016-2020","article-title":"The era of CFTR modulators: Improvements made and remaining challenges","volume":"16","author":"LaSelva","year":"2020","journal-title":"Breathe"},{"key":"ref_3","unstructured":"(2022, July 20). 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