Gene Lost, Autism Gained

Loss of the Contactin 4 Gene May be Responsible for Some Cases of Autism

by Dr. Barry Starr, Stanford University

March 21, 2008

A new study claims that the contactin 4 gene is important in some cases of autism. The researchers believe this because 3 out of 92 people with autism in their study had lost one of their two copies of this gene.

Contactin 4 makes sense as an autism gene since it is involved in setting up and running the brain. And if autism is anything, it is a disorder of the brain.

People with autism seem to sense the world differently than people without the disorder. Because of this, they have trouble communicating with other people and often prefer to be alone.

But there isn't just one autism. Autism is a spectrum disorder which means someone with autism can have a wide range of possible symptoms.

Some people with autism are socially awkward. Some become entirely withdrawn. And some hurt themselves or others.

The evidence that autism is partly genetic is pretty strong. The evidence for contactin 4 is less so.

But this preliminary study now opens the way for additional studies on this gene. If the results hold up, they may lead to a diagnostic test that will let doctors identify infants with autism at an earlier stage when the doctors can provide more help. And maybe knowing the contactin 4 gene is involved will lead to a new autism treatment.

The Evidence for Autism Genes is Strong

Identical twin studies
show that genetics play
a big role in autism.

Scientists have known for awhile that autism is partly genetic. How do they know?

First off, it tends to run in families. If parents already have a child with autism, the risk that another child will get it too is somewhere between 2 and 10%. And if the parents have two kids with autism, the third has a whopping 35% chance at autism. Both of these chances are much higher than in the general population where 1 in 150 people have autism.

Twin studies also point to genes being important. Identical twins have the same DNA. And they usually both end up with autism.

Various studies have shown that if one identical twin has autism, the other does 60-90% of the time. This compares to fraternal twins where the percentage is somewhere between 0 and 10%. (Fraternal twins only share as much DNA as any two siblings.)

Since both twins in an identical twin pair get autism so much more often that both twins in a fraternal pair, genes are very important. But the 60-90% number tells us that genes aren't everything. If they were, then the number would be 100%.

In any event, these studies point to genes being involved in autism. Scientists have had trouble finding these genes though. Now, this new study may have found one of them in contactin 4.

Contactin 4 Partly Explains Some Cases of Autism (Maybe)

The new study looked at the DNA of 92 people with autism. These people's symptoms ranged from mild to severe.

The results showed that three of the 92 people had a change on chromosome 3. By looking more closely at this region, they found that part of the DNA had duplicated itself in one case. And that in the other two, DNA was removed.

In both cases, the DNA change caused the contactin 4 gene to stop working. In the deletion case, the gene was simply removed.

In the duplication case, the DNA duplicated itself in the middle of the gene. This broke the contactin 4 gene into two nonworking pieces.

Obviously the loss of contactin 4 doesn't explain all cases of autism. For example, 89/92 cases in this study did not have big changes in this gene*.

Contactin 4 does not
explain all cases
of autism.

Even more important than this, losing one copy of the contactin 4 gene does not mean that someone will get autism for sure. In all three cases, the dad had the DNA change in his genes and passed it down to his kids. But the dads didn't have autism.

There are a couple of possibilities here. One is that the dads had a mild form of autism that had gone undetected. In this case, the loss of the contactin 4 gene leads to autism but something else leads to how severe that something is.

This "severity factor" could be another gene. Or something in the environment.

Another possibility is that loss of the contactin 4 gene isn't enough. In other words, you need to have other genes affected too.

So there is still a lot to do to really nail down this gene as important for autism. Especially given that the study was such a small one.

Researchers need to confirm that losing a copy of the contactin 4 gene causes autism. They also need to look for smaller changes in this gene that might also lead to autism. And finally, they need to do a larger study that looks at more people including folks without autism.

This study gives researchers a great place to start though. And if contactin 4 does prove to be important, it might point scientists towards a new diagnostic test or even a new treatment. We'll need to wait and see.

*Although the study did not look for smaller changes which might have been there so we can't know this for sure.

More Information

Why Losing One Gene Copy Can Cause Problems

Remember, DNA is really just a set of instructions written out in a four letter code. Each gene has a set of instruction for making a single protein. The gene has the instructions for how to make the protein. And when, where and how much of it to make.

So the contactin 4 gene makes just the right amount of contactin 4 protein in all of the right places. And this protein goes about setting up and running the brain.

Anything that changes the instructions might change something with the protein. And this might cause problems.

The loss of one copy of the gene means that the people only have one working copy*. So they will end up making less of the protein.

The idea would be that making less protein means that the brain gets set up and run differently. And this difference is what causes autism symptoms. Or at least that's the theory.

*We have two copies of most of our genes--one from mom and one from dad.

Content provided by the Department of Genetics, Stanford University.