Cystic Fibrosis Gene Undetected In Screening Of Infertile Men

Dr. Keith Jarvi, an associate professor of surgery at the University of Toronto and staff urologist at Mount Sinai Hospital, led a study showing that a significant number of infertile men have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and many of these genetic defects go undetected in routine screening for cystic fibrosis.

"Dramatic advances in surgery and in vitro fertilization have given many men with infertility an opportunity to father children, which they could not have done 20 years ago," says Jarvi. "But we're now finding out that we may be putting some of these children at a higher risk of being born with cystic fibrosis."

The routine CFTR screening panel is designed to detect the 31 most common gene mutations associated with CF in the Caucasian population, leaving many of the less common mutations undetected. There are over 800 known mutations associated with CF.

Researchers studied 130 men with three different forms of infertility: congenital bilateral absence of the vas deferens (CBAVD) where men are missing both the vas deferens -- the tube that carries sperm out from the testes -- and tubing around the prostate; congenital unilateral absence of the vas deferens (CUAVD) where one of the tubes is missing and the other is obstructed; and idiopathic, or unknown, obstruction of the epididymis, the tube outside of the testes where sperm are stored and mature.

The panel failed to identify 46 per cent of detectable CFTR mutations in the CBAVD group, 50 per cent in the CUAVD group and 79 per cent of mutations in the idiopathic group. Jarvi stresses that while the routine panel is still effective for detecting cystic fibrosis in the general population, it should be used cautiously in patients with infertility.

In addition to improving screening methods for men, Jarvi suggests testing women for gene mutations, noting the reduced likelihood of a severely affected child when only one of the parents tests positive. "We have to be more knowledgeable about the kind of genetics we're dealing with before we start offering the reproductive technology. We need to know the risks."

Usually detected in childhood, cystic fibrosis affects about one in 2,000 Canadians and is one of the most common hereditary diseases in North America. The study was funded by the National Institutes of Health, the Canadian Cystic Fibrosis Foundation, the Canadian Genetics Diseases Network and the Canadian Urology Association. The results will be presented at an American Medical Association media briefing on genetics on Thursday, June 10, 1999 in San Francisco.