Embryos tested for haemophilia gene mutation

Dr. Kirsty Horsey

Progress Educational Trust

18 July 2005

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[BioNews, London]

UK scientists have used preimplantation genetic diagnosis (PGD) to help a couple conceive a baby unaffected by haemophilia, a serious inherited blood clotting disorder. A team at the Clinical Sciences Centre in Hammersmith, London and colleagues at Queen Charlotte's Hospital used a new test that directly detects the gene mutation responsible, allowing unaffected male and female embryos to be identified. Previously, PGD for haemophilia involved discarding all male embryos, since only boys are affected by the condition.

PGD can be carried out on IVF embryos, to ensure that only those unaffected by a particular genetic condition are returned to the woman's womb. It has been used since 1989 to test for diseases where the single gene involved has been identified (for example cystic fibrosis), and for disorders caused by mutations in X-chromosome genes. In the case of haemophilia and many other X-linked conditions, only boys are usually affected - the harmful effects of the mutated gene are masked by a working copy in girls, who have two X-chromosomes. Until now, PGD to avoid an X-linked condition involved testing embryos for the presence of a Y-chromosome, to identify male embryos. However, 50 per cent of these male embryos would be unaffected by the disorder.

In the latest case, reported by the Daily Telegraph, doctors used the new haemophilia test to help Debbie and Steve Hunter conceive an unaffected baby. Mrs Hunter is a carrier of haemophilia A, the most serious form of the disease, and her ten-year-old son Ben is affected by the condition. It is caused by a mutation in the Factor VIII gene, which makes a protein involved in blood clotting. All boys born to carrier women have a 50 per cent chance of being affected, while all girls will be unaffected. However, any girl born to a carrier mother has a 50 per cent chance of being a healthy carrier herself.

The Hunters underwent two cycles of IVF treatment, and the resulting embryos were tested for the presence of the mutation. 'We had two embryos suitable for return, one normal (either boy or girl) and one female who carried the disease', said team leader Professor Tuddenham. Both were implanted, one of which resulted in the birth of a healthy baby girl, Grace, who is now 12 weeks old. It is not yet known whether Grace is a carrier of the disease herself, but Professor Tuddenham says that 'we now have the means to end haemophilia in an affected blood line'. Mrs Hunter describes Grace as 'like any other normal baby. She is lovely, really lovely'.

The new test should lead to greater success rates when carrying out PGD for haemophilia, says team member Stuart Lavery. He explained that this is because there is a greater chance of having better quality embryos to transfer, since doctors can choose from a pool of 75 per cent of the embryos produced by the couple instead of 50 per cent. It also means that patients will potentially have the opportunity to have an unaffected son, as well as unaffected daughters. 'As the technology of single cell analysis becomes increasingly sophisticated, I expect that specific mutation analysis will replace embryo sexing for all X-linked conditions', Dr Lavery told BioNews.