{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:34:07Z","timestamp":1760060047089,"version":"build-2065373602"},"reference-count":77,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"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\/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in other geographical regions. The aim of our retrospective study was to present the genetic variants identified in a group of 48 CF patients from the Moldova region (Romania), as well as to establish genotype\u2013phenotype correlations. Methods: Genetic testing was initially performed for 38 CFTR mutations, and in heterozygous patients or those in whom no mutation was detected, CFTR gene sequencing (NGS) was performed. Results: The compound heterozygous genotype was identified in 26 (54.16%) of the patients (with one of the alleles being F508del), while 22 (45.83%) patients had the homozygous F508del genotype. The F508del variant was the most frequent (69.79%), followed by G542X (6.25%, 6\/96). Several new variants were also identified that had not been reported in other studies from Romania (R1158X, K598*, R347H, c.2589_2599del, R496H, and CFTRdele2). Phenotypic manifestations in patients with CFTR class I, II, III and VII variants (homozygous and compound heterozygous) were more severe compared to those in patients with CFTR class IV, V and VI mutations, with the data obtained being consistent with those in the literature. Respiratory tract involvement was present in 77.08% of the patients, being more frequent in patients with the compound heterozygous genotype compared to the homozygous F508del genotype. Most patients had exocrine pancreatic insufficiency (EPI) (85.41%). Gastrointestinal manifestations included hepatocytolysis (66.66%) and biliary cirrhosis (0.41%). Meconium ileus was detected in 18.75% of patients, all with a compound heterozygous genotype. Conclusions: We compared the results obtained with data from the literature and correlated the detected CFTR variant (genotype) with the phenotypic manifestations, highlighting certain particularities present in some patients. Genetic testing allows for early diagnosis and adapted management, including personalized treatment for each patient. Identification of novel unclassified CFTR variants still remains a challenge for clinicians. NGS-based screening of heterozygous healthy carriers is important for both genetic counseling and prenatal diagnosis.<\/jats:p>","DOI":"10.3390\/jcm14155362","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T16:16:10Z","timestamp":1753805770000},"page":"5362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Heterogeneity Correlated with Phenotypic Variability in 48 Patients with Cystic Fibrosis"],"prefix":"10.3390","volume":"14","author":[{"given":"M\u0103d\u0103lina Andreea","family":"Donos","sequence":"first","affiliation":[{"name":"Department of Mother and Child, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6713-4244","authenticated-orcid":false,"given":"L\u0103cr\u0103mioara Ionela","family":"Butnariu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8657-378X","authenticated-orcid":false,"given":"Dana Teodora","family":"Anton P\u0103duraru","sequence":"additional","affiliation":[{"name":"Department of Mother and Child, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina Mariela","family":"Murgu","sequence":"additional","affiliation":[{"name":"Department of Mother and Child, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Rusu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6762-4067","authenticated-orcid":false,"given":"Monica Cristina","family":"P\u00e2nzaru","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2183-0690","authenticated-orcid":false,"given":"Roxana","family":"Popescu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3018-8011","authenticated-orcid":false,"given":"Elena","family":"\u021aarc\u0103","sequence":"additional","affiliation":[{"name":"Department of Surgery II\u2014Pediatric Surgery, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u015fi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7859-840X","authenticated-orcid":false,"given":"Elena","family":"Cojocaru","sequence":"additional","affiliation":[{"name":"Department of Morphofunctional Sciences I, Grigore T. Popa University of Medicine and Pharmacy, 700115 Ia\u015fi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Ghiga","sequence":"additional","affiliation":[{"name":"Department of Mother and Child, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-7610","authenticated-orcid":false,"given":"Laura Mihaela","family":"Trandafir","sequence":"additional","affiliation":[{"name":"Department of Mother and Child, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"unstructured":"(2025, March 06). Online Inherithance of Man (OMIM). Available online: https:\/\/omim.org\/entry\/602421?search=CFTR&highlight=cftr.","key":"ref_1"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.medcli.2023.06.006","article-title":"Cystic fibrosis: Epidemiology, clinical manifestations, diagnosis and treatment","volume":"161","year":"2023","journal-title":"Med. Clin."},{"unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2025, March 07). 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