Autism And Mutations: UBE3A Also Linked To Rare Neurological Disorder Angelman Syndrome

First Posted: Aug 07, 2015 12:26 PM EDT

The Centers for Disease Control and Prevention (CDC) reveals that 1 in 68 children in the United States will be diagnosed with an autism spectrum disorder (ASD), with the behavioral health issue affecting a higher number of boys than girls.

As researchers learn more about what's responsible for the health issue, new findings published in the journal Cell show how one specific mutation contributes to autism. While studying the development of a rare neurological disorder known as Angelman syndrome, the study authors found that they could potentially reverse the symptoms of the neurodevelopmental disorder. 

While researachers have identified more than 1,000 gene mutations in individuals with autism, just how the mutations increase such a risk remains relatively unclear. 

While studying Angelman syndrome, a genetic disorder that results in developmental disabilities and neurological problems, including difficulty speaking, balancing and walking, researchers noticed mutations near the gene responsible for regulating the enzyme UBE3A that is important for neural function and brain development, and which has been thought to be a cause of autism as this genetic mutation can be seen in those with the condition.

In Angelman, though, the mutations delete the enzyme in people; the mutations in autism, on the other hand, cause it to be doubled or tripled.

Using an autistic child's cell lines from the Simons Simplex Collection, researchers found the gene mutation turns off the switch tightly controlling UBE3A. The researchers sequenced genes from the child's parents' cell samples, finding the parents did not have the mutation that the child did.

"When this child's mutation was introduced into an animal model, we saw all these dendritic spines form on the neurons," said Dr. Mark Zylka, an associate professor of cell biology and physiology at the University of North Carolina, in a press release. "We thought this was a big deal because too many dendritic spines have been linked to autism."

To help explain it a bit further, in those with autism, duplication of the 15q chromosome region, also referred to as Dup15q syndrome, is one of the most common genetic abnormalities that was previously believed to be the cause of too much UBE3A.

Yet in normal brain development, the UBE3A gene can be turned off through the attachment of a phosphate molecule that acts as a regulatory switch, according to Medical News Today.

However, researchers found that mutations in UBE3A destroy the regulatory switch that they identified via kinase A (PKA), resulting in hyperactivity of the gene, which then causes autism.

Researchers concluded that there may be a way to decrease UBE3A via drugs that control the protein kinase A. In fact, two compounds were seen in the lab to "substantially" reduce the enzyme's activity in neurons. However, more research will be needed. 

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