Dr. Raphael Bernier

Dr. Raphael Bernier

A researcher at Seattle Children’s Hospital and Research Institute, in collaboration with researchers from 13 institutions worldwide, has found a genetic identifier for autism that includes physical features and a pattern of symptoms that may eventually allow clinicians to develop targeted treatments or ultimately potentially identify babies who are at risk for autism before they are born.

Dr. Raphael Bernier, clinical director of Seattle Children’s Autism Center and Associate Professor at the University of Washington, discovered that a mutation of the CHD8 gene, in addition to significantly increasing a child’s risk of developing a specific subtype of autism, also causes several unique physical traits.

We had the opportunity to chat with Bernier and ask him how this discovery will impact children and families.

Why did you begin looking at genetic causes of autism and how did you find this specific mutation?

This discovery is the result of years of research aimed at improving care for children with autism. Every child with autism is different and unique. As a clinician, that makes it difficult to determine the best treatment. For a long time, we tried to group children together based on their behaviors, but that was not effective. So, we started looking to group kids together based on their genetics.

Led by Evan Eichler’s team at UW, we first studied a couple hundred children with autism and identified several gene mutations that we believed were playing a causal role. Based on these findings, we estimated about 800 genes were likely to play a role in autism. That was overwhelming. It seemed like every child had a different genetic mutation that could be causing their autism. But when we expanded our research to include thousands of kids, and focused on specific genes, we started to see reoccurring disruption of the CHD8 gene.

We found two patients in Washington State with the CHD8 mutation and asked them to visit the clinic. The first was a 12-year-old girl with specific autistic behaviors, a prominent forehead and wide-set eyes. She had trouble sleeping and was frequently constipated. When I met the second patient, an 8-year-old boy, I could not believe the similarities. He looked as though he could have been her brother. Same head shape, same eyes and same sleep and gastrointestinal issues. That’s when I thought – maybe this is a significant subtype.

How did you confirm your hypothesis?

We started by collaborating with zebrafish experts. An outside institution genetically modified zebrafish – a commonly used animal model with much of the same DNA as humans – with the CHD8 mutation. Like the patients I had met, the fish had large heads and wide-set eyes. When they fed them fluorescent pellets, the fish even experienced constipation.

Is this the first time researchers have found a genetic cause of autism?

Since the late 1970s, from twin studies, we’ve know autism has a genetic component. There have been previously identified gene mutations, like Fragile X, which account for a greater number of autism cases, but are more often associated with other impairments, such as intellectual disability, than autism. Although less than half a percent of kids with autism will have the CHD8 mutation, it is likely one of the most common single gene causes. And there are other genetic contributors as well, such as chromosomal structural changes. Like most single gene mutations, these structural changes are associated with many disorders in addition to autism.

How will this discovery improve the lives of children with autism and their families?

Although it’s preliminary, now that we know children with theCHD8 gene mutation have common facial features and a high risk of developing autism, it is possible that in the future clinicians will be able to use this information to screen babies while they are still in utero and potentially confirm the genetic mutation. Physical and genetic indicators are already used to detect other disorders like Down Syndrome.

Early detection is critical in the treatment of autism symptoms. Research studies of behavioral therapies used with younger siblings of kids with autism, who are at higher risk for developing autism themselves, suggest that intervention between 3 to 6 months of age may lessen or even prevent symptoms from developing. The goal is to be able to use these same exercises on babies with a higher risk of autism who have been identified before birth. We know that if we can intervene by 3 or 6 months of age instead of later in life, we can help the child learn important social communication skills, like eye contact.

Tell us more about the gastrointestinal symptoms experienced by children with the CHD8 mutation. How will this impact their care?

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 appear to be the result of the CHD8 disruptions.

How will this impact future autism research?

This will be a game changer in the way scientists are researching autism. Children with autism are incredibly diverse. We need a better understanding of who we are studying. This research provides strong evidence that we cannot group all kids with autism together. We must determine genetic causes of different subtypes to find effective treatments.

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