Decades’ long search for a possible cause of autism finally came to some fruition with scientists discovering that mutation in a specific gene called CHD8 causes a subtype of this neurodevelopmental disorder. The discovery of this gene may have great potential for developing autism-specific interventions.

"We finally got a clear cut case of an autism specific gene," said Raphael Bernier, in a press release. He is the lead author and University of Washington associate professor in the Department of Psychiatry and Behavioral Sciences and the clinical director of the Autism Center at Seattle Children's.

People who carry the mutated variant of the CHD8 gene have a very strong likelihood of having autism marked by a similar cluster of symptoms including gastrointestinal disorders, a larger head, and wide set eyes. The results of the study, carried out in collaboration with 13 institutions around the world, were published in Cell magazine under the title "Disruptive CHD8 Mutations Define a Subtype of Autism in Early Development."

The researchers studied 6,176 children with autism spectrum disorder and found that 15 of them had a CHD8 mutation. These children had distinct facial characteristics, gastrointestinal complaints, and sleep disturbances. To confirm that mutation in the CHD8 gene was responsible for these traits, the team worked with scientists at Duke University who use zebra fish modelling to study several human diseases.When scientists disrupted the CHD8 gene in fish embryos, the fish ended up having increased head size and wide set eyes. The fish also developed gastrointestinal problems as they took much longer to move fluorescent pellets along their digestive tracts compared to controls. In short, the fish were constipated.

Bernier said this is the first time researchers have shown a definitive cause of autism due to a genetic mutation. Although genetic mutation in the Fragile X gene is most commonly associated with autism, it is characterized mainly by developmental and intellectual disorders. With only a handful of cases identified so far, mutations in CHD8 seem rare, according to Bernier. But identifying a specific subtype of autism will greatly help in developing specifically designed treatments. Treatments for autism have not achieved significant breakthroughs due to the heterogeneous nature of the condition. There are only a few known causes of it and it may be caused by mutations to any of the countless genes in the human body.

Some of the known genetic events related to autism are chromosomal re-arrangements or copy number variation where one or more sections of the DNA are either copied or deleted. But no one rearrangement affects more than 1 percent of all autism cases. But scientists have not been able to definitively prove the association between these copy number events and autism. The other known event is mutation in the DNA that alters the function or production of specific proteins which may lead to autism.

The discovery of the CHD8 mutation as a clear link to autism can now be used as a stepping stone to uncover several other genetic issues related to autism. Diagnosis can then be based on these underlying conditions rather than on behavior alone. Most of all, it can be used to develop drugs for specific sub-types of autism.

Source- Bernier R, Golzio C, Xiong B,, Disruptive CHD8 Mutations Define a Subtype of Autism in Early Development, Cell, 2014.