Phenotypic impact of CFTR mutations on male reproductive tract agenesis in a Chinese cohort with congenital absence of the vas deferens

To investigate the genotype-phenotype correlations of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and their impact on male reproductive tract development in a cohort of Chinese patients with congenital absence of the vas deferens (CAVD). A total of 121 Chinese CAVD patients underwent genetic testing for CFTR and ADGRG2 mutations, semen analysis, scrotal and transrectal ultrasound examinations, and reproductive hormone measurements. The genotype-phenotype correlations were analyzed, focusing on the impact of CFTR variants on the presence or absence of the epididymis, vas deferens, seminal vesicles, and other related structures. CFTR mutations were identified in 72.7% (88/121) of CAVD patients, with the IVS9-5 T variant being the most prevalent (54.5%, 66/121). Six novel CFTR variants (CFTR: L218Ffs*15, V1007Ffs*40, V938M, A566V, S605P, H949P) were identified in Chinese men. Patients with CFTR homozygous IVS9-5 T variants had a significantly lower rate of epididymal absence compared to those with one 5 T and one non-5 T variant or two non-5 T variants (p = 0.016). Notably, patients carrying at least one non-5 T variant were associated with an 8.17-fold increased risk of epididymal partial absence compared to those having the homozygous 5 T mutation (95% confidence interval 1.52-59.58, p = 0.009). This study provides novel insights into the genotype-phenotype correlations of CFTR variants in Chinese CAVD patients, highlighting the differential impact of 5 T and non-5 T variants on male reproductive tract development. These findings provide additional information that may be helpful for genetic counseling, clinical management, and the development of personalized diagnostic and therapeutic strategies for CAVD patients.