Genotype-phenotype correlation of CFTR variants in cystic fibrosis patients
RESPIRATORY MEDICINE, cilt.260, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 260
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.rmed.2026.108925
- Dergi Adı: RESPIRATORY MEDICINE
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Health Research Premium Collection (ProQuest)
- Kocaeli Üniversitesi Adresli: Hayır
Özet
Introduction: Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder caused by mutations in the CFTR gene. In Turkiye, high genetic diversity and consanguinity contribute to a heterogeneous CFTR variant spectrum; however, genotype-phenotype data remain limited. Methods: This retrospective study analyzed 92 Turkish CF patients (36 homozygous, 56 compound heterozygous) to characterize CFTR variant diversity and clinical outcomes. Next-generation sequencing (NGS) was performed and confirmed by Sanger sequencing. Clinical data were analyzed using chi-square and nonparametric tests (p < 0.05). Results: A total of 46 distinct CFTR variants were identified. The most frequent were F508del (24%), followed by Y515X (7.33%), G542X (6%), N1303K (5.33%) and D110H (4%). Meconium ileus (p = 0.017) and CF-related diabetes mellitus (p = 0.013) were significantly more frequent among homozygous patients. Pseudomonas aeruginosa and Staphylococcus aureus were the most prevalent pathogens. CFTR modulator therapy eligibility was significantly higher among compound heterozygous patients (p = 0.007). Non-missense variants were associated with higher sweat chloride levels and more frequent severe pancreatic insufficiency and abnormal fecal fat quantification compared with missense variants (p = 0.037; p = 0.001; p = 0.033). Conclusion: This study highlights the heterogeneous CFTR variants in Turkiye and suggests genotype-phenotype correlations. Homozygous patients tended to show more severe gastrointestinal and endocrine involvement, while compound heterozygotes may exhibit comparatively milder disease features and higher treatment eligibility.