Wellcome Trust Centre For Mitochondrial Research

Mitochondrial DNA Defects


Mitochondrial DNA abnormalities are present in many patients with mitochondrial disease. This does present difficult dilemmas for women with mitochondrial DNA mutations because only women with mutations pass on the disease to their children. We can be quite confident that men do not pass on the mutation and therefore there is no risk to the offspring of a man who either carries a mitochondrial DNA mutation or has mitochondrial DNA disease. There are a variety of possibilities for women with mitochondrial DNA disorders, a number of which are being tested experimentally at the present. For an outline of some of the options available to women please see the video below


Genetic counselling

Since mitochondrial DNA is transmitted from mother to child, the offspring of mothers with mitochondrial DNA mutations are at risk of developing the same disease. However, it is very important to realise that the risk to offspring varies considerably from one mutation to another. For some, such as the mutation which causes Leber’s hereditary optic neuropathy, there is usually transmission of the mutation from mother to child whereas in patients with mitochondrial DNA single deletions there is rarely transmission of the mutation from mother to child. It has to be stressed that even though a mitochondrial DNA mutation may be transmitted to the child this does not necessarily mean that the child will develop mitochondrial disease.

It is recommended that mothers with mitochondrial DNA mutations who want to have children should seek specialist advice if they are at all concerned about the possibility. The specialist’s advice should come from doctors who have experience of counselling specifically about mitochondrial genetic disorders.

Oocyte donation

There is now the possibility for mothers with mitochondrial DNA mutations to consider receiving an egg (oocyte) donation. Oocyte donation is when an egg from an unrelated female is fertilised by your husband or partner’s sperm and that this egg is then implanted into your womb. This means that the baby will not have any mitochondria from you, only from the donor female. This is certainly a way in which to prevent the transmission of mitochondrial disease. At present in most countries there is a shortage of donor eggs. This means there can be quite a long waiting list for a technique like oocyte donation. It does also involve the lady undergoing an IVF procedure.

Chorionic villous sampling and amniocentesis

Chorionic villus biopsy and amniocentesis are two techniques in which cells, which derive from the baby are tested to see whether or not the baby carries the mitochondrial DNA mutation. These techniques are used quite extensively for nuclear genetic disorders or abnormalities of the chromosomes such as Down’s syndrome. These two techniques are done at different stages during a pregnancy and are both fairly safe procedures. The real difficulty here is that there is no point in undergoing one of these procedures with the attendant discomfort and risks involved if you would not consider having a termination.

Another major problem with these techniques is the difficulty for doctors to predict the outcome for the child even if the child carries the mitochondrial DNA mutation. At present there have been very few studies where this has been done for mothers with mitochondrial DNA mutations and it is our belief that this should still only be done in very specialised centres.

Pre-implantation genetic diagnosis

This is a new technique, which is also used for nuclear genetic disorders. This involves the patient undergoing in-vitro fertilisation (IVF) and a single cell from the developing embryo is actually removed and undergoes genetic analysis prior to the embryo being implanted back into the woman’s womb. This technique is also highly specialised and as far as we are aware has only been applied to one individual female by a group in Paris. It is certainly a feasible technique for patients with mitochondrial DNA disorders, but should still be regarded as experimental in view of the fact that there has been so little experience with it. The ideal would be that if several embryos are generated during the IVF procedure only embryos in which there is either no mitochondrial DNA mutation or very low amounts of the mitochondrial DNA mutation would be implanted back into the lady’s womb. This could either prevent or severely limit the chance of the child developing mitochondrial DNA disease.

Development Of New Techniques

One area in which there is very active research is trying to prevent the transmission of mitochondrial DNA disease. The idea here is to take a woman’s egg (or an egg just after fertilisation) and transfer the nuclear genetic material into another unrelated egg, from which only the nuclear genetic material has been removed. Thus with the transfer, all the nuclear genetic information for the baby would be present, but it would be transferred into an egg which would have different mitochondrial genetic background and thus the mitochondrial DNA mutation would either be absent in the developing baby or present at very low levels.

This is very much a research based technique which has been proven to be successful in experiments both in Canada and in Japan on mice that carry a mitochondrial DNA mutation. In the UK permission has been granted to allow research on human eggs, but even if this research was successful in the laboratory, at present this could not be used on patients until there is a change in the Law in the UK.