Tuesday, May 8, 2007

On the cause of autism.

A new Nature Medicine (subscription requried) "News & Views" article by Art Beaudet at Baylor College of Medicine summarizes some new discoveries about autism. As it turns out, somewhere between 10-30% of autism patients can be demonstrated to have de novo mutations (i.e. occurring in the sperm or egg) that cause their symptoms. This is cool work, as two different groups found copy number changes in 10-30% of autism patients that wasn't present in the parents. Why is this cool? Because it answers a longstanding question:

Autism is thought to be highly heritable, largely because of a very high concordance in monozygous (identical) twins—although the concordance in dizygous (fraternal) twins is low.
One would expect the frequency to be lower in fraternal twins, but for autistic patients, this was lower than normal. Well:
All of the genetic abnormalities discussed here would be expected to be associated with virtually 100% concordance in monozygotic twins and, for the de novo majority, very low concordance in dizygotic twins ... ... Thus, for a fraction of cases, this new understanding of the genetic etiology of autism fits perfectly with the previously puzzling data from twins.
So, if many of the changes are mutations occurring in the sperm or eggs, one would expect identical twins to have the same disease, as they would both carry the mutation. But the odds of both fraternal twins getting sperm or eggs that carry a brand new mutation are astronomical.

Beaudet hypothesizes two things:
Higher density arrays focused at the level of single exons are likely to be very productive in identifying smaller abnormalities that may be immediately traceable to specific genes.
That is, once we look more closely, it may turn out that an even higher percentage of autism patients are due to de novo mutations. And second:
Our view is that epigenetic abnormalities of chromatin that are not associated with nucleotide sequence changes might contribute to the etiology in this group; particularly given the male predominance, epigenetic abnormalities affecting the X or Y chromosome might be hypothesized. We have proposed a mixed epigenetic and genetic and mixed de novo and inherited model for autism, in which individual patients could have a genetic (mutation) or epigenetic (epimutation) etiology and these components could be inherited in some cases and de novo in others.
He suggests that epigenetic factors will prove to be important for other patients, that is that improper modification of chromosomes in the mother or father, will be the causative agent. Though to be fair, he says:
an epigenetic component, if one exists, remains elusive
Nonetheless, we are now discovering the cause of autism in some patients. Now, some important questions remain. Are the sites that are mutating de novo particularly susceptible to mutation? Or are other sites that mutate just less important? And importantly, what do these sites tell us about the pathology of autism? And can we design treatments and diagnostic tests to find and help autism patients? Can we find the cause of autism in other autistic patients?

This paper raises the possibility that we could know the causes of all autism in the near future. Very exciting, indeed!

Digg!

3 comments:

Ted said...

What of the recent assertions of autism caused by rainy weather and TV?

More causation/correlation?

The Factician said...

I hadn't heard that one. I haven't managed to track down the paper to see if there's any value in it. However, one of the assumptions that they are making is that autism rates have increased over time. I think that most researchers looking at this problem think that diagnoses are going up, but that the actual rates may be static (they're just being recognized more often). But your article certainly raises some interesting questions...

Ted said...

Well, there's also this in the NYT from last week:

Child Care: Regular Television Time Starts for Many at 3 Months

For many families, apparently, it is never too early to watch television. Researchers reported yesterday that 40 percent of infants are regular viewers of television or videos by age 3 months, and 90 percent are watching regularly by age 2.

The researchers interviewed more than 1,000 parents in February 2006, and found that the average amount of viewing time for all children up to 2 years was a little more than 40 minutes a day. Among 2-year-olds, an average day included more than one and a half hours of TV.


The study on all this TV watching is here:

Seems interesting that the first study implies that some genetic trigger is in play relative to development.