Pending diagnosis

Question

Hello,
Following two semen analyzes showing azoospermia, I performed a testicular ultrasound which revealed bilateral absence of the vas deferens and a genetic analysis of the CFTR gene.
I received the first "transient" results indicating that I carry the F508del mutation. My blood sample has been sent to a second laboratory to search for rare mutations.
Do I necessarily carry a second mutation on the other allele? Is it also possible for me to carry a mutation that could not be detected by the current techniques of genetic analysis?

Answer

Hello,
It is known that 80–90% of men with congenital absence of the vas deferens (CBAVD) carry at least one CFTR mutation and 50–60% have two CFTR mutations (see Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice, Journal of Cystic Fibrosis 2008, Castellani et al.).
It is therefore not surprising that you carry one mutation. The F508del mutation is the most common mutation, found in 40% of men with CBAVD, followed by the 5T variant in about 35%. R117H was also frequently reported (about 30%) in these patients.
For those men with 2 CFTR mutations, usually one is CF-causing (such as F508del), and the other is a CFTR-related disorder associated mutation. CFTR-related disorders include CBAVD, acute recurrent pancreatitis, sometimes isolated sinusitis or bronchiectasis. In these cases, there is no pancreatic insufficiency (which causes fatty diarrhea with abdominal pain), nor a classic CF lung disease (with chronic cough, purulent sputum, bronchial infections and progression to respiratory failure).
In very rare cases, the diagnosis of CBAVD leads to a diagnosis of CF with two "severe" mutations. Those are men who had prior respiratory symptoms whose cause had not been identified.
A second CFTR mutation is not always found in CBAVD, but it is yet impossible to know whether this is related to the lack of current genetic diagnostic techniques.
Best regards.
Dr Dominique Hubert

22.05.2012