Genetic link to autism known as CHD8 mutation discovered – sciencedaily


In a collaboration involving 13 institutions around the world, researchers have innovated to understand the causes of autism. The results are published in Cell magazine July 3, 2014: “Disruptive CHD8 mutations define a subtype of autism during early development. “

“We finally got a clear case of a gene specific for autism,” said Raphael Bernier, senior author and associate professor at UW in the Department of Psychiatry and Behavioral Sciences and clinical director of the Seattle Children’s Autism Center.

Bernier said people who carry a mutation in the CHD8 gene have a very “high probability” of having autism marked by gastrointestinal disturbances, a larger head and splayed eyes.

In their study of 6,176 children with autism spectrum disorders, the researchers found that 15 had a CHD8 mutation and that all of these cases had similar characteristics in terms of appearance and sleep disturbances and gastrointestinal issues.

Bernier and his team interviewed the 15 cases carrying CHD8 mutations.

To confirm the results, the researchers worked with scientists at Duke University who model zebrafish. The researchers disrupted the CHD8 gene in the fish, and the fish developed a large head and splayed eyes. They then fed the fish with fluorescent pellets and found that the fish had difficulty shedding food waste and were constipated.

Bernier said it was the first time researchers have shown a definitive cause of autism to a genetic mutation. Genetic events previously identified as fragile X, which account for a greater number of autism cases, are associated with other impairments, such as intellectual disability, more than autism. Although less than half a percent of all children have this type of autism linked to the CHD8 mutation, Bernier said the study has many implications.

“It will be a game-changer in the way scientists study autism,” he said.

The results could pave the way for a “genetics-driven approach” that could uncover hundreds of additional genetic mutations and lead to genetic testing. Genetic testing could be offered to families to guide them on what to expect and how to care for their child. Currently, autism is diagnosed based on behavior, Bernier said.

In the short term, said Bernier, clinicians can pay attention to the small population with this CHD8 mutation and provide targeted therapy.

Researchers say autism is currently linked to different types of genetic events. The most commonly studied genetic events associated with autism are chromosomal rearrangements, called “copy number changes”, in which a piece of the chromosome is copied or deleted. But no rearrangement affects more than 1% of all autism cases. Although these copy number events are associated with autism, they do not have a definitive link, or as they say among researchers, “strong penetrance.”

Then there are genetic mutations in which a gene has been disrupted and does not create the type of protein it should make. The mutation of the CHD8 gene is the first mutation in the gene to show a very strong penetrance linked to a certain subtype of autism.


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