In addition, some infrequent mutations have been identified in the ubiquitin-specific protease 9, Y-linked (USP9Y) and the synaptonemal complex protein 3 (SYCP3) gene that cause azoospermia.
Five individuals with heterozygous pathogenic CFTR variants were identified using targeted NGS in a cohort of 1112 idiopathic infertile men with azoospermia or severe oligozoospermia.
Clinical evidence shows increased mutation frequency or reduced CFTR expression in men with congenital bilateral absence of vas deferens (CBAVD) or sperm abnormalities, such as azoospermia teratospermia and oligoasthenospermia.
All subjects affected by obstructive or secretory azoospermia should undergo molecular analysis and counselling for CF using gene scanning which has a high detection rate and also reveals rare CFTR mutations.
Extended CFTR mutation screening was performed in 310 infertile men (25 with congenital absence of the vas deferens (CAVD), 116 with non-CAVD azoospermia, 169 with severe oligospermia), 70 female partners and 96 healthy controls.
These results underline the importance of performing molecular analysis of mutations and IVS8-Tn polymorphism in the CFTR gene and appropriate genetic counselling to all couples undergoing assisted reproductive technologies when the partner has azoospermia or severe oligozoospermia.
Chromosome aberrations, Y chromosome microdeletions and CFTR (cystic fibrosis transmembrane conductance regulator) mutations alone may explain up to 25% of azoospermia and severe oligozoospermia.
To present the first case of an infertile male with azoospermia related to a congenital bilateral absence of the vas deferens (CBAVD), in which mutations within the cystic fibrosis transmembrane conductance regulator (CFTR) gene coexist with a robertsonian translocation.
CFTR gene mutations were commonly seen in men with congenital absence of the vas deferens, but also in 16% of men with azoospermia without any apparent abnormality of the vas deferens.
To provide better insight into the relationship among the expression behavior in vivo of the three genes in human testis, analysis of MDR1 and MRP gene expression in testicular biopsies was performed and related to the presence of CFTR gene mutations in congenital absence of the vas deferens (CAVD: n = 20) and non-CAVD (n = 30) infertile patients with azoospermia or severe oligozoospermia.
Seminal plasma characteristics as indicators of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in men with obstructive azoospermia.
None of the CFTR mutations were observed in patients with azoospermia without CAVD or with severe oligozoospermia and the frequency of allele 5T was 3.6% (three out of 78 alleles) and 1.35% (one out of 74 alleles) respectively.
This increased frequency of CF mutations in healthy men with reduced sperm quality and in men with azoospermia without CBAVD suggests that the CFTR protein may be involved in the process of spermatogenesis or sperm maturation apart from playing a critical role in the development of the epididymal glands and the vas deferens.