The child with the epilepsy-related SCN1A mutation also inherited from his mother a deletion that increases the risk for epilepsy; and indeed, that child has been diagnosed with epilepsy. The findings support the 'multi-hit' theory of autism, the idea that it may take a combination of mutations in the same pathway to cause severe autism or related disorders.
Studying 20 families is just a start "a teaser," as Eichler puts it. At the same time, the study offers two important proofs of principle: It provides compelling evidence that de novo point mutations may underlie many cases of autism, and it shows that exome-sequencing is an effective way to discover which of the more than 20,000 genes in the human genome are responsible for autism spectrum disorders.
"It's like having a dartboard with 20,000 candidates the fact that we could pick off four outstanding candidate genes is a great success," Eichler says. "It's proof on the ground that this technique is fruitful."
The Simons Foundation is providing funding for Eichler's team and several other groups to do whole-exome sequencing of several hundred families in the Simons Simplex Collection over the next few months. As whole-exome and eventually whole-genome sequencing become more accurate and affordable, it won't be long before it will be possible to sequence several thousand families, which should be enough data to provide statistical arguments about which genes are responsible for autism spectrum disorders, Eichler says.
"Within a couple of years, we should have a pretty comprehensive view
|Contact: Anastasia Greenebaum|