Screening of ΔF508 mutation and IVS8-poly T polymorphism in CFTR gene in Tunisian infertile men without CBAVD

Abstract

It is well established that cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations are involved in congenital bilateral absence of the vas deferens (CBAVD), causing obstructive azoospermia and male infertility. Also, several studies reported a relatively high prevalence of CFTR gene mutations in healthy men presenting reduced sperm quality. In this study, we investigate ΔF508 mutation and IVS8-polyT polymorphism in CFTR gene in Tunisian infertile men without CBAVD. Genetic analyses were performed in 148 infertile patients and 126 fertile individuals. The polymorphic IVS8-polyT tract in CFTR gene was analysed in only 129 infertile patients and 54 individuals of control group. As well, we screened for Y chromosome microdeletions in all infertile patients. No ΔF508 mutation was diagnosed either in infertile patients or in control group. 5T allele of IVS8-polyT tract was found in both infertile men (4.26%) and fertile individuals (8.33%). 5T/5T genotype was observed only in two azoospermic patients without Y microdeletions. The most frequent genotype of IVS8-polyT tract in infertile men and controls was 7T/7T (69.75% and 59.25% respectively). There was no association between IVS8-polyT polymorphism and reduced semen quality. Neither ΔF508 mutation nor 5T allele is involved in pathogenesis of male infertility in Tunisian infertile patients without CBAVD.

Meta-analyses of 4 CFTR variants associated with the risk of the congenital bilateral absence of the vas deferens

“…CBAVD is responsible for 1-2% of male infertility [1]. CBAVD was widely considered as an atypical symptom of cystic fibrosis (CF, MIM: #219700) [2,3], which was a severe recessive disease characterized by obstructive chronic lung disease, pancreatic disease and abnormal concentrations of electrolytes in the sweat in clinical studies [4]. Approximately 97% of the male CF patients also suffered from CBAVD [5].…”

“…Another common variations, IVS8-Tn, had three forms containing five, 7 seven, or 9 nine thymidine residues in this locus, which is considered an incomplete penetrance [14]. The 5T allele especially produces high levels of CFTR transcript without exon 9, resulting in variable phenotypes which were observed in CBAVD or mild CF patients [4]. Experimental evidence indicates that 5T carriers have a decreased splicing efficiency of intron 8 [15,16].…”

CFTR Deletion in Mouse Testis Induces VDAC1 Mediated Inflammatory Pathway Critical for Spermatogenesis

“…It is well established that Caucasians are more likely to develop classic CFTR disease and show a higher mutation rate, such as 508 mutation, compared with Chinese and other east Asian populations [ 3 ]. A recent study showed that the 5T haplotype is relatively more common compared with fertile controls, indicating that same mutation of CFTR may be shared with different ethnicities [ 6 , 9 , 35 , 36 ]. Several studies have shown that IVF patients have more 5T mutations; therefore it has been recommended that a CFTR mutation screen should be conducted in IVF clinics as routine practice.…”

Preimplantation genetic diagnosis for cystic fibrosis: a case report

“…(9) This gene codifies a protein expressed in apical membrane of exocrine epithelia cells. (10) Mutations in CFTR gene produce an variable phenotype, including pulmonary disease, pancreatic disease, meconium ileus (11) and they are also involved in bilateral agenesis of the vas deferens, causing obstructive azoospermia and male infertility (12) (Figure 3). …”

“…(9) Esse gene codifica uma proteína expressa na membrana apical das células epiteliais exócrinas. (10) Mutações no gene CFTR produzem um fenótipo variável, incluindo doença pulmonar, insuficiência pancreática, íleo mecônio (11) e também estão envolvidas na agenesia bilateral dos ductos deferentes, causando azoospermia obstrutiva e infertilidade masculina (12) (Figura 3). …”