An analysis of cystic fibrosis transmembrane conductance regulator gene variants in the Cystic Fibrosis Registry of Türkiye

Capraz Yavuz, Burcu; Kara, Ali; DAYANGAÇ ERDEN, DİDEM; Sen, Velat; Selimoglu Sen, Hadice; Oztosun, Berrak; Korkmaz, Cigdem; Ayzit Kilinc, Ayse; Savas, Suat; Ercan, Fatih; Koşak, Sevde; Karcioglu, Oguz; Gulen, Figen; Kartal Ozturk, Gokcen; CANITEZ, YAKUP; Korkmaz, Merve; Talip, Mey; Kose, Mehmet; Ersoy, Ali; Ademhan Tural, Dilber; Yetisgin, Hande; Keskin, Ozlem; Inal, Gaye; HANGÜL, Melih; Dagdelen, Erdi; Bingol, AYŞEN; Basaran, ABDURRAHMAN; Ozdemir, Ali; Polat Yulug, Demet; Serbes, Mahir; Altintas, Derya; Kekeç, Handan; Aslan, Ayse; ÖZSEZEN, BESTE; Ramasli Gursoy, Tugba; ÇOBANOĞLU, FATMA; Korkmaz, Pervin; Yuksel, Hasan; ANIL, HÜLYA; GAYRETLİ AYDIN, ZEYNEP; Asfuroglu, Pelin; Çaltepe, Gönül; DEMİRDÖĞEN, EZGİ; Kılıc, Mehmet; Topal, Erdem; Hizal, Mina; Cakir, Eylul; Ikizoglu, Nilay; Nayir Buyuksahin, Halime; ZİREK, FAZILCAN; Ocak, Ece; Cakir, Erkan; Sismanlar Eyuboglu, Tugba; Cinel, Guzin; Pekcan, Sevgi; EMİRALİOĞLU ORDUKAYA, NAGEHAN; DOĞRU ERSÖZ, DENİZ; Ozcelik, Ugur

doi:10.1007/s00431-026-07498-x

An analysis of cystic fibrosis transmembrane conductance regulator gene variants in the Cystic Fibrosis Registry of Türkiye

Capraz Yavuz B., Kara A. S., DAYANGAÇ ERDEN D., Sen V., Selimoglu Sen H., Oztosun B., ...Daha Fazla

European Journal of Pediatrics, cilt.185, sa.11, 2026 (SCI-Expanded, Scopus)

Yayın Türü: Makale / Tam Makale
Cilt numarası: 185 Sayı: 11
Basım Tarihi: 2026
Doi Numarası: 10.1007/s00431-026-07498-x
Dergi Adı: European Journal of Pediatrics
Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
Anahtar Kelimeler: CFTR modulators, CFTR variants, Cystic fibrosis, Genetic diversity, National registry, Precision medicine, Translational research
Akdeniz Üniversitesi Adresli: Evet

Özet

This study aimed to characterize the CFTR variant spectrum in Türkiye and the variants identified in people with cystic fibrosis (pwCF) without current elexacaftor/tezacaftor/ivacaftor (ETI) reimbursement. This nationwide registry-based study used 2023 data from the Cystic Fibrosis Registry of Türkiye. ETI reimbursement status was assessed according to the current national reimbursement criteria. All CFTR variants identified in pwCF without ETI reimbursement were evaluated according to their functional characteristics and available supporting evidence. Among 2258 pwCF, 2071 had at least one identified CFTR variant. F508del accounted for 22.0% of CFTR alleles. ETI was not reimbursed for 649 pwCF. Among pwCF without ETI reimbursement, 68 (10.4%) had only one identified CFTR variant. Of 581 pwCF with two identified variants, 376 (64.7%) had two established Class I variants, 35 (6.0%) had two probable Class I variants, 31 (5.3%) were homozygous for exceptional Class I variants, and 63 (10.8%) had two likely non-Class I variants. A total of 44 pwCF were homozygous for R334W, 4096-3C > G, 3849 + 5G > A or 1898 + 3A > G, or carried one of these variants in trans with a Class I variant. Additionally, 18 pwCF without reimbursement for either ETI or vanzacaftor/tezacaftor/deutivacaftor (VTD) had a variant included in the FDA-approved VTD label, either homozygously or in trans with a Class I variant. Twenty pwCF in our cohort were homozygous for CFTR variants demonstrating an in vitro response to VTD exceeding the ≥ 10% of wild-type CFTR function threshold. Conclusion: Nearly one-third of genetically characterized pwCF in Türkiye were without ETI reimbursement, reflecting the heterogeneous CFTR variant spectrum. Differences between regulatory indications, national reimbursement criteria, and CFTR modulator responsiveness may contribute to disparities in treatment access. (Table presented.)