PGD for familial hypercholsterolaemia approved

20 December 2007

The UK Human Fertilisation and Embryology Authority (HFEA) has granted a licence to University College Hospital in London, permitting pre-implantation genetic diagnosis (PGD) for familial hypercholesterolaemia (FH), an inherited condition typified by very high levels of low-density lipoprotein (LDL) cholesterol and early onset cardiovascular disease (see HFEA statement).


The most severe form of FH is caused by the presence of two copies of disease-associated variants of the LDL-R (LDL receptor) gene; homozygotes for this variant have very serious disease that can be fatal in childhood or early adulthood. However, PGD could also identify embryos that are heterozygous (have only one copy of) a disease-associated variant; this generally causes a milder form of FH, which is treatable with drugs and an appropriate dietary regimen, and which is thought to affect as many as one in every 500 individuals in the UK. However, the HFEA has restricted the licence to selection against embryos with the homozygous, more serious form of the condition only.


Presumably this means that only embryos identified with two copies of the disease-linked genetic variant may be disposed of, and no distinction may be made between embryos that are entirely free from the FH-linked variant (and would be disease-free), and those that are heterozygous for the disease variant and would be affected by the milder form of FH. Some would suggest that it is unethical to fail to select the healthiest embryos to implant (as part of the in vitro fertilisation process); others have expressed concern at the possibility of screening out embryos that will not be affected by a serious form of disease.


The couple on whose behalf the licence application has been made are both heterozygous carriers with mild FH, who have a homozygous daughter with severe FH, as well an unaffected son. They are quoted as saying: “We had no idea that we both carried a gene for high cholesterol until the double gene was expressed in our first child. We are very lucky that our child has responded so well to the very high-dose drug regime. We have been led to understand that other children with the same double gene may not be so lucky” (see Times report).

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