Embargo: 13.00 hrs CET Monday 28 June 1999

Diagnostic advance could prevent CF in children of nearly 90 per cent of couples at risk

A new technique with the potential to prevent cystic fibrosis in the babies of nearly
90% of couples carrying defective CF genes was reported today (Monday 28 June) by Dutch researchers.

The technique involves pre-implantation genetic diagnosis (PGD) which means that couples who both carry CF mutations could opt to use IVF procedures instead of natural conception, have the embryos tested for CF and have only a healthy embryo transferred to the woman's uterus.

The technique is now ready for introduction in the clinic. Mr Jos Dreesen from the Academic Hospital in Maastricht, said that it would be an alternative to the current situation where prenatal diagnosis offered many woman only the choice between giving birth to a CF child or having an abortion.

He told the annual conference of the European Society of Human Reproduction and Embryology in Tours, France, that more than 700, mostly rare mutations, had been identified worldwide in the CF gene. About 60% of Dutch CF couples had the most common mutation and a test for this change in embryonic cells was already established. But for the other 40% no PGD was available and developing tests for specific mutations was practically impossible.

Dreesen and colleagues have instead developed a PGD protocol based on testing markers linked to the CF gene - a process known as indirect detection. This was more generally applicable and independent of the specific mutations in the carriers.*

"It means that the CF status of more than 90% of embryos will be able to be determined with a reliability of over 99.95% using our new marker-based PGD protocol," he said. "This in turn means it is a generally applicable alternative for the current specific mutation-directed protocols and suitable for 87% of all couples where both partners are CF carriers."

Cystic Fibrosis is a common inherited disorder affecting many bodily functions including breathing, digestion and reproduction. In CF the glands that produce mucus, saliva and intestinal fluids do not work properly. Abnormal mucus clogs the lungs and leads to breathing problems, pulmonary damage and life-threatening infections. It also obstructs the pancreas preventing enzymes from reaching the intestines to help break down and digest food. Men are usually infertile and woman have reduced fertility. Twenty years ago many CF patients were not expected to reach school-age but better treatment means that, today, average life expectancy has risen to about 30.

CF occurs in about one in 2,500 live births among Caucasians and one in 25 is a symptomless carrier of the defective gene. In the USA alone, there are more than 10 million carriers and each year more than 1,000 babies are born with CF. To develop CF, a child must inherit two defective copies of the gene, one from each parent. Each time two carriers conceive there is a 25% chance the child will have CF, a 50% chance the child will be a symptomless carrier and a 25% chance it will be unaffected.

Mr Dreesen concluded: "It is distressing enough for a couple to know that they have a one in four chance of a baby having CF. It is doubly distressing if pre-natal tests for those for whom no PGD was available show the child is affected: they then have to opt to have a disabled child or an abortion. Our new technique means we can now offer most couples a way to avoid such a painful decision."

Note: * PGD involves removing a single cell from an 8-cell embryo to test for CF. Only unaffected embryos are transferred. Technically it is a major challenge as all genetic analyses have to be performed on the single cell within a very tight time frame.

The protocol developed by the Maastricht team involved using four closely linked markers, two on each side, of the CF gene, which is on chromosome 7. To achieve a diagnosis with 99.95% reliability it is necessary to use at least two flanking markers, one on each side of the CF gene and this will be possible in about 87% of the couples. The marker testing yielded a result in more than 99% of the analyses. In 5-10% of the cells the results could not be interpreted unambiguously for various reasons, and in those cases embryos would not be transferred.
Abstract no: O-075

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