Genotype-phenotype correlation of CFTR variants in cystic fibrosis patients

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. © 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.