Genetics and Aicardi-Goutières syndrome !

Genetics and Aicardi-Goutieres syndrome

The occurrence of Aicardi-Goutieres syndrome in brothers and sisters, and the observation of an increased number of families where the parents are blood relatives to one another, suggests that Aicardi-Goutieres syndrome is a genetic disease.

We inherit genetic material (DNA) from our parents in small packets called genes. Genes come in pairs - one member of every pair from our mother via the egg and the other member of the same pair from our father via the sperm.

There are some genetic conditions, such as Aicardi-Goutieres syndrome, where a child inherits a non-functioning copy of a gene from each parent so that they have a 'double-dose' of the non-functioning gene and are affected with the disease; this is called autosomal recessive inheritance.

The parents themselves have one non-functioning and one normally functioning copy of the gene. The presence of the normal copy is enough to prevent them having the disease and parents are sometimes called 'carriers'.

When two people who are carriers for Aicardi-Goutieres syndrome have children there is a 1 in 4 chance of having an affected child. This 1 in 4 risk applies to each pregnancy.

Although we don't know exactly how common Aicardi-Goutieres syndrome is it is probable that approximately 1 in 100 people are carriers for the condition. The chance of any 2 people in the general population having a child with Aicardi-Goutieres syndrome is small (i.e. 1/100 x 1/100 x 1/4) but the risk is increased where the couple are blood relatives since if there is a non-functioning copy of the gene in a family it may be passed down to both parents from a common ancestor.

 


The results of the genetic studies carried out so far in Aicardi-Goutieres syndrome suggest that more than one gene can cause the disease. It might be that there are several genes involved in a common biochemical pathway essential for normal brain development and damage to both copies of any one of these genes could 'block' that pathway and cause Aicardi-Goutieres syndrome; so-called 'genetic heterogeneity'. Although this might sound surprising it is in fact a common genetic phenomenon but the problem is it makes gene identification more difficult than when only one gene is involved.

The first step in identifying the gene for a genetic condition is to 'localise' it to a specific position on a particular chromosome (chromosomes are large packages of genetic material containing many hundreds of genes). This is done by looking at the DNA from families with the condition.

The next step is to pin-point the exact gene from the many genes which might be present in that chromosome region and identify changes (mutations) in the gene which could be responsible for its inability to function properly.

These last 2 steps can be very difficult but the large amount of genetic data that is becoming available through the Human Genome Project will help enormously in this work.

 


written by Dr. Crow (England)