Williams Syndrome FISH Test Explained

If you are living or working with someone who you suspect has Williams Syndrome, the chances are that you’ll be talking with a medical specialist about this at some stage soon.

You may discuss the typical signs and symptoms of Williams Syndrome and you can certainly read our other articles on this site.

It won’t be long before the doctor tells you that the gold standard in diagnostic tests for Williams Syndrome is the FISH test.

At this point you would be forgiven for thinking that they’re beginning to lose the plot. What does Williams Syndrome have to do with FISH?!

Please allow me a few more minutes to explain some of the technicalities behind this genetic test.

FISH Test For Williams Syndrome

You may already know that human cells contain DNA and this is organised into 23 different chromosomes encoding or carrying our genes. In most cells in our body these chromosomes come in pairs. So we have 23 pairs of chromosomes (numbered 1 through to 23) and within each pair, one comes from Dad and one from  Mom. This means that we have two copies for most of our genes, one paternal copy, one maternal copy which are not identical but are very similar versions of the same thing. The tiny differences between one copy and another, between copies in different people, are what makes each individual, well, an individual. The final pair of chromosomes may be different to each other as they are the sex chromosomes that determine whether we are a male (X and Y) or a female (X and X) human being.

Each chromosome has many hundreds of different genes organised like beads on a string. The chromosome affected in Williams Syndrome is chromosome 7 and the number of genes on chromosome 7 is likely to be more than 1,000 but less than 1,4000 genes.

In someone with Williams Syndrome, at some stage, probably during the formation of the egg or sperm cell, a small piece of chromosome 7 was lost. If chromosome 7 has 1,000 genes, a person with Williams Syndrome has lost just 25 or so genes from only one of their two copies of chromosome 7. This tiny difference is enough to cause what we know as Williams Syndrome.

The gene that lies at the center of this deletion is the gene for a protein called Elastin. Elastin is an important protein in forming a specific type of muscle, making that muscle more elastic. While elastin was the first gene to be identified as missing in the Williams Syndrome deletion, it is not the only gene missing and, in ‘classical’ Williams Syndrome between 20 and 30 genes are missing which contribute to the other characteristic symptoms of the syndrome.

So where does the FISH test come in?

Because the Williams Syndrome deletion is so small, it’s impossible to see the difference in the size of an affected chromosome by looking down a microscope. Therefore we need another type of test.

The name FISH test, is a very specific technical name meaning Fluorescent In Situ Hybridisation. You really don’t need to know what this means in detail but what it means in practice is we can make a small piece of DNA to use as a probe, like a piece of bait or a fishing hook. I will explain the detail in another video for you but let’s just get the general idea here!

The probe is designed to seek out and stick to the normal copy of elastin on chromosome 7. In order to be able to see this DNA, we can use chemicals to paint it a particular color so it fluoresces or shines in the dark. When we look down the microscope now, we don’t notice the size of the chromosome as much as we see the color glowing when the probe binds.

In the FISH test you can imagine making a probe which is designed to detect only the elastin gene. If it does, and it binds to the elastin gene on chromosome 7, it glows pink.

When samples of DNA extracted from a small blood sample from someone with Williams Syndrome is tested with this elastin FISH probe, the remaining single copy of the elastin gene glows pink.

But, the scientists like to make doubly sure before they make a diagnosis – and how can you be certain you have only one copy of elastin and not the normal two copies?

One way is to make a different FISH probe to another gene on a totally different part of chromosome 7 which isn’t involved in the Williams Syndrome deletion. If you label this FISH probe green and mix the pink and green probes together then what you get is an amazing picture.

When these are used to stain a normal cell from someone without Williams Syndrome and two perfectly normal copies of chromosome 7, you see two green spots and two pink spots.

Photograph showing FISH results for Williams SyndromeThe DNA from someone affected by Williams Syndrome shows two green spots (the unaffected part of chromosome 7) and only one pink spot (the second pink spot is absent as the elastin gene on the second copy of chromosome 7 is missing).

Does everyone with Williams Syndrome symptoms give this typical result in the FISH test?

Well, it is possible to imagine that the chromosomal deletion removes some of the associated genes in the ‘classical’ Williams gene block, leaving enough of the elastin gene to bind to the FISH probe so giving a false result with two green spots and two pink spots.

In theory, such a person could show some of the symptoms of Williams Syndrome. If this happens at all, it is likely to be even more rare than the classical Williams Syndrome deletion event and I personally don’t know of anyone affected in this way. You may of course!

Equally it is possible for someone to have a defect or a deletion just affecting the elastin gene. If tested, such a person might give the typical result, two green spots and only one pink spot, but they wouldn’t actually have Williams Syndrome. However, lacking a copy of the elastin gene they would probably show symptoms such as aortic stenosis which many Williams people also show.

As is often the case with genetics, the answer is, it’s complicated.

So that’s it!

That’s what it means to have a micro deletion of genes from chromosome 7 and why the FISH test is the gold standard for diagnosis of Williams Syndrome.