27 Diagnosing cystic fibrosis: Neonatal screening versus clinical diagnosis. A national registration

Abstract

Objectives: Obstructive azoospermia is present in the greatest majority of male patients with Cystic Fibrosis (CF), mainly because of congenital bilateral absence of the vas deferens (CBAVD). The aim of this study was to identify the presence of CFTR gene mutations in Portuguese adult infertile males, clinically diagnosed with CBAVD, CUAVD, azoospermia and other clinical reasons of infertility. Methods: The CFTR gene analysis was performed in 105 patients, using ARMSAmplification Refractory Mutation System, RDB-Reverse Dot-Blot (INNO-LiPA CFTR19 and 17+Tn update), DGGE-Denaturing Gradient Gel Electrophoresis) and DNA sequencing, detecting about 93% of the mutations associated to CF in the Portuguese population. Conclusion: In the group of patients clinically diagnosed with CBAVD/CUAVD/ Azoospermia (82/105): CFTR mutations were found in 60% (2 mutations in 33% and 1 mutation in 27%). The most frequent CF mutation was c.1521_1523delCTT (F508del) in 32% of the patients and the poly-T variation c.1210−12T[5] (IVS8−6(5T)) was found in 40%. The most frequent genotype was c.[1521_1523delCTT];[1210−12T[5]] (F508del/IVS8−6(5T)) present in 23% of the patients. In the remaining infertile patients (23/105) the frequency of CFTR mutations was similar to the general population. Although the clinical diagnosis is not very specific, we were able to detect a high frequency of CF carriers. It’s important to analyze these men in assisted reproduction programs to prevent new cases of CF.