CHD8 Genetic mutation genetic mutation may lead to an autism subtype

A paper published in Cell Journal on July 3 hints that a mutation in the  regulation gene CHD8 may be the closest Scientific explanation yet to the onset of autism.

Chief author Evan Eilrich, Professor of genome science in the University of Washington, has been investing his time in looking for genetic mutations that he thinks are “autism hotspots” which started with his revolutionary research into the Fragile X gene mutation FMR1.

People with CHD8 mutation have similar characteristics. A large forehead and distinctive facial characteristics, one of the strongest links is the vast majority of people with the mutation also have autism.

Autism is notoriously heterogeneous, perhaps involving mutations in any of hundreds of genes. Typically, researchers begin by studying people with similar symptoms and working backward to identify what causes those symptoms. But that approach has not been particularly productive.

Lead researcher of the study, Professor of Psychiatry at Washington State University Raphael Bernier told Scientific American :

“We’ve tried for so long to identify subtypes of autism based on behaviour alone and we’ve done abysmally at that.”

So in this study, they have done exactly the reverse. Look at a group of people with the same genetic mutation, and then characterise their symptoms to see if there were any similarities.

The relationship was suggested in early 2012 but only on a small group of children with the mutation. This study took 3,730 children with autism and developmental delay and identified eight mutations in the sequencing of the gene. There were no mutations in any of the 9000 controls.

Early detection is critical in the treatment of autism symptoms. Research studies of behavioural therapies used with younger siblings of kids with autism, who are at higher risk for developing autism themselves, suggest that intervention between three to six months of age can lessen or even prevent symptoms from developing. The goal, Raphael Bernier said, is to be able to use these same exercises on babies with a higher risk of autism who have been identified before birth.

The study, titled “Disruptive CHD8 Mutations Define a Subtype of Autism Early in Development,” followed 6,176 children with autism spectrum disorder for nine months. Researchers found that 15 had a CHD8 mutation and that all of those cases had similar characteristics in appearance as well as issues with sleep disturbance and gastrointestinal problems including constipation.

Bernier and his team interviewed all 15 cases with CHD8 mutations, and confirmed the findings by working with scientists who study zebrafish, a tropical freshwater fish commonly used in research because of its regenerative abilities. Researchers disrupted the CHD8 gene in the fish, which then developed large heads and wide set eyes. They then fed the fish fluorescent pellets and found that the fish also were constipated and had problems discarding food waste.

“For years, parents of children with autism have been telling us the gastrointestinal symptoms are real, but science has been slow to respond. Now, we have clear evidence that in a subgroup of individuals with autism, both the autism symptoms and constipation are a result of the CHD8 disruptions. This will be a game changer in the way scientists are researching autism,” he said. “Children with autism are incredibly diverse so we must determine the genetic causes of different subtypes to find effective treatments.”