Congenital Bilateral Aplasia of the Vas Deferens, CBAVD - CFTR

CBAVD

Clinical Features

Approximately 2% of all infertile men have genetically caused alterations of the spermatic duct: A congenital bilateral aplasia of the vas deferens (CBAVD) or, less frequent, a congenital unilateral aplasia of the vas deferens (CUAVD). The CBAVD results in male infertility. Sterility can be treated by intracytoplasmic sperm injection (ICSI), following scrotal biopsy or following isolation of single sperm from the ejaculate. It is therefore suggested that men who have CBAVD should be considered for CF screening prior to ICSI treatment. Aplasia of the vas deferens is observed in cystic fibrosis (male CF patients are infertile), may be an isolated finding, or may be part of a syndrome together with additional malformations of the kidneys or the urinary tract.

Genetic Information

The CFTR gene (cystic fibrosis transmembrane conductance regulator gene) underlying cystic fibrosis is located on chromosome 7 (7q31.2). Cystic fibrosis (CF, mucoviscidosis) follows autosomal recessive inheritance. Isolated CBAVD (without concomitant kidney/urinary tract affection) is a minor form of cystic fibrosis and frequently associated with mutations in the CFTR gene.

However, the mutational spectrum diverges significantly from that of typical CF patients:

In 33% of men with CBAVD, two mutations in the CFTR gene are detected (besides the mutation F508del which is frequent in Middle Europe e.g. the mutation R116H or the 5T allele);
56% carry one genetic defect (CFTR mutation or 5T allele),
in 11% of the male patients there is no mutation detectable.

In the flanking region of exon 9 of the CFTR gene (in intron 9) there is a repeat of 7 or 9 thymidine nucleotides (polyThymidine tract). In patients with CBAVD this repeat can be shortened to 5 thymidines (so-called 5T allele or 5T variant) leading to reduced levels of the CFTR protein.

Prevalence

Approximately every 22nd to 25th person within the normal population is a healthy carrier of one mutation in the CFTR gene, approximately 5% of the normal population carry a 5T allele. These carrier rates are much higher in men with CBAVD (see above).