Dr. Raphael Bernier

Dr. Raphael Bernier

Dr. Raphael Bernier, clinical director of the Autism Center and investigator in the Center for Child Health, Behavior and Development at Seattle Children’s Research Institute has continued his quest to identify genetic mutations that are linked to autism. In a new paper published in Nature Genetics, Bernier and his collaborators at the University of Washington discovered evidence that some children with autism were more likely to have inherited gene mutations most often occurring from mothers to sons.

On the Pulse sat down with Bernier to learn more about these exciting findings.


Q: You’ve been researching the genetics of autism for years now, what’s new about your findings?
A:In 2014 we discovered a mutation of the CHD8 gene that, in addition to significantly increasing a child’s risk of developing a specific subtype of autism, also causes several physical traits and symptoms that are unique to children with the same subtype of autism.

At that point, we were comfortable stating that we had identified the genetic contribution for roughly 30-45% of all individuals diagnosed with autism. That is, for 30-45% of individuals with autism we could identify de novo gene changes (changes that the parents did not have) that were contributing to the development of autism. But that still led us to wonder about what the genetic contributions were for the other individuals with autism.

Our current research has led us to identify inherited, protein-truncating mutations. We found mutations in children with autism that were inherited from parents. These mutations were most often inherited from the mother, suggesting females may “harbor” such mutations before passing them on to an affected son.

If the mother carries the gene mutation, there is a chance she will pass the disruption to her children, and if that child is male he will likely develop autism, but if that child is female, she is less likely to.

Q: What are the odds a boy will inherit the gene from the mother?
A: We estimate roughly 10 percent of all patients with autism have these types of inherited mutations we’ve identified. With this discovery, in addition to those de novo genes that have previously been identified, we can now claim we’ve found the genetic contribution for 50% of all children that have autism.

Q: Why aren’t girls with these gene mutations developing autism?
A: We don’t know yet. There is definitely a protective factor about being female. We hope to learn more about this now that we’ve identified these mutations.

Q: How did you accomplish this study?
A: In 2007 The Simons Foundation Autism Research Initiative brought our group together to research autism. The funding they provided allowed us to start collecting data from 2,800 families. The data was uploaded in repository so all group members could access it for autism research.

In this specific study I collaborated with lead authors Drs. Eichler, Krumm and Turner from the University of Washington to analyze the genetic profiles of 2,377 families with at least one child with autism and one or more children without the condition (neither parent had autism, either). We created genetic profiles for each participant by sequencing the protein-coding portions of their genomes.

Q: How will all of this affect the lives of patients with autism and their families?
A: The abnormal proteins we’ve discovered will be important in the search for future therapies and treatments for autism. At the end of the day, I want to identify biomarkers that will speed up the diagnostic process and allow us to find interventions that are specific to a particular child. We are setting the stage for personalized medicine and developing targeted medications for the gene mutations.

We’ve come so far since the initial autism research done in the 1950s, but we still have all these misconceptions about what causes it. I want to be able to provide families with answers regarding their child’s diagnosis. I hope we can begin to take away the fear and guilt parents sometimes have associated with their child’s autism.

Q: What do you love most about your work?
A: It has been so rewarding to be able to provide this kind of information to parents. We can now connect families who have children with the same genetic disruptions. They work together to share what works for their family and provide support to one another.