Congenital bilateral absence of the vas deferens (CBAVD) - CFTR gene
Congenital bilateral absence of the vas deferens (CBAVD), also known as congenital aplasia of the vas deferens, is a common cause of obstructive azoospermia, which accounts for approximately 2% of infertility cases male. CBAVD is a hereditary disease of the mucous glands, and it is mostly found in men affected by cystic fibrosis, characterized by causing chronic progressive damage to the respiratory and digestive systems. Although many men with CBAVD do not have the other characteristic features of cystic fibrosis, some affected may have mild digestive or respiratory problems.
CBAVD is due to mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene in more than half of the cases. This gene is a regulator of transmembrane conductance of cystic fibrosis. In cases of CBAVD without a mutation in the CFTR gene the reason for this alteration is unknown. Some cases are associated with other structural abnormalities of the urinary tract. When CBAVD is due to mutations in CFTR and has no characteristics of cystic fibrosis, the condition is considered a form of atypical cystic fibrosis.
The CFTR gene is located on the long arm of chromosome 7 (7q31.2), and includes 24 exons with a size of 250 kb that give rise to an mRNA of 6,500 bp. This gene encodes a protein (CFTR) of 1,480 amino acids and 168 kDa molecular weight. CFTR is a chlorine channel regulated by the cAMP that regulates other ion channels. The CFTR maintains the hydration of secretions in the vas deferens by transporting chlorine and inhibiting sodium uptake. The CFTR protein also regulates the function of other channels, such as those that transport sodium ions through cell membranes. These channels are necessary for the normal function of organs such as the lungs and pancreas.
At least 80 mutations in the CFTR gene have been identified in men with CBAVD. These mutations disrupt the function of the chloride channel, preventing the normal flow of chloride and water ions inside and outside the cells. As a consequence, male genital tract cells produce abnormally thick and sticky mucus. This mucus clogs the vas deferens as they develop, causing them to deteriorate before birth. Sperm cannot be transported from the testicles to be included in semen without the vas deferens. Males affected by this disorder are infertile, unless they resort to assisted reproduction techniques. Cystic fibrosis and CBAVD are, in any case, two distinct clinical entities.
Cystic fibrosis -see Cystic fibrosis - CFTR gene- is a potentially fatal disease that was diagnosed in the first years of life because of the pulmonary and gastrointestinal manifestations and developmental problems with which it is associated. In contrast, CBAVD is usually diagnosed in adulthood due to infertility problems in generally healthy adults.
When the congenital bilateral absence of the vas deferens (CBAVD) is due to mutations in the CFTR gene, it is inherited with an autosomal recessive pattern. This pattern of inheritance means that both copies of the gene in each cell must have mutations for the alteration to be expressed. Affected men who choose to have children through assisted reproduction have a higher risk of their offspring developing cystic fibrosis. If the congenital absence of the vas deferens is not due to mutations in the CFTR gene, the risk of having children with cystic fibrosis is not increased.
Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with congenital bilateral absence of the vas deferens (CBAVD), by means of the complete PCR amplification of the exons of the CFTR gene, and their subsequent sequencing.
Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leukocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).