Scientists find connection between gene mutation, key symptoms of autism

April 25, 2014, The Scripps Research Institute

Scientists have known that abnormal brain growth is associated with autism spectrum disorder. However, the relationship between the two has not been well understood.

Now, scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown that mutations in a specific gene that is disrupted in some individuals with autism results in too much growth throughout the , and yet surprisingly specific problems in social interactions, at least in mouse models that mimic this risk factor in humans.

"What was striking is that these were basically normal animals in terms of behavior, but there were consistent deficits in tests of and recognition—which approximate a major symptom of autism," said Damon Page, a TSRI biologist who led the study. "This suggests that when most parts of the brain are overgrown, the brain somehow adapts to it with minimal effects on behavior in general. However, brain circuits relevant to are more vulnerable or less able to tolerate this overgrowth."

The study, which focuses on the gene phosphatase and tensin homolog (PTEN), was recently published online ahead of print by the journal Human Molecular Genetics.

Autism spectrum disorder is a neurodevelopmental disorder involving a range of symptoms and disabilities involving and communication difficulties, repetitive behaviors and interests, and sometimes cognitive delays. The disorder affects in approximately one percent of the population; some 80 percent of those diagnosed are male.

In a previous study, Page and colleagues found that mutations in Pten causes increased brain size and social deficits, with both symptoms being exacerbated by a second "hit" to a gene that regulates levels of the neurotransmitter serotonin in the brain. In the new study, the TSRI team set out to explore whether mutations in Pten result in widespread or localized overgrowth within the brain, and whether changes in brain growth are associated with broad or selective deficits in tests of autism-relevant behaviors in genetically altered mice. The team tested mice for -related behaviors including mood, anxiety, intellectual, and circadian rhythm and/or sleep abnormalities.

The researchers found that Pten mutant mice showed altered social behavior, but few other changes—a more subtle change than would have been predicted given broad expression and critical cellular function of the gene.

Intriguingly, some of the more subtle impairments were sex-specific. In addition to social impairments, males with the mutated gene showed abnormalities related to repetitive behavior and mood/anxiety, while females exhibited additional circadian activity and emotional learning problems.

The results raise the question of how mutations in PTEN, a general regulator of growth, can have relatively selective effects on behavior and cognitive development. One idea is that PTEN mutations may desynchronize the normal pattern of growth in key cell types—the study points to dopamine neurons—that are relevant for social behavior.

"Timing is everything," Page said. "Connections have to form in the right place at the right time for circuits to develop normally. Circuitry involved in social behavior may turn out to be particularly vulnerable to the effects of poorly coordinated growth."

Explore further: Study shows gene defect's role in autism-like behavior

More information: "Pten Haploinsufficient Mice Show Broad Brain Overgrowth but Selective Impairments in Autism-Relevant Behavioral Tests," hmg.oxfordjournals.org/content … /hmg.ddu057.abstract

Related Stories

Study shows gene defect's role in autism-like behavior

August 10, 2012
Scientists affiliated with the UC Davis MIND Institute have discovered how a defective gene causes brain changes that lead to the atypical social behavior characteristic of autism. The research offers a potential target for ...

Low doses of antianxiety drugs rebalance the autistic brain

March 19, 2014
New research in mice suggests that autism is characterized by reduced activity of inhibitory neurons and increased activity of excitatory neurons in the brain, but balance can be restored with low doses of a well-known class ...

The gene family linked to brain evolution is implicated in severity of autism symptoms

March 21, 2014
The same gene family that may have helped the human brain become larger and more complex than in any other animal also is linked to the severity of autism, according to new research from the University of Colorado Anschutz ...

Diagnosing and treating autism

April 18, 2014
April is National Autism Awareness Month. The Child Development Clinic at Children's Hospital of Richmond at VCU (CHoR) provides comprehensive assessment for pediatric patients with developmental delays or disabilities, including ...

Surprising new insights into the PTEN tumor suppressor gene

April 24, 2014
Ever since it was first identified more than 15 years ago, the PTEN gene has been known to play an integral role in preventing the onset and progression of numerous cancers. Consequently, when PTEN is either lost or mutated, ...

Recommended for you

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Being bilingual may help autistic children

January 16, 2018
Children with Autism Spectrum Disorders (ASD) often have a hard time switching gears from one task to another. But being bilingual may actually make it a bit easier for them to do so, according to a new study which was recently ...

No rise in autism in US in past three years: study

January 2, 2018
After more than a decade of steady increases in the rate of children diagnosed with autism in the United States, the rate has plateaued in the past three years, researchers said Tuesday.

Autism therapy: Brain stimulation restores social behavior in mice

December 13, 2017
Scientists are examining the feasibility of treating autistic children with neuromodulation after a new study showed social impairments can be corrected by brain stimulation.

Social phobia linked to autism and schizophrenia

December 11, 2017
New Swinburne research shows that people who find social situations difficult tend to have similar brain responses to those with schizophrenia or autism.

Odors that carry social cues seem to affect volunteers on the autism spectrum differently

November 27, 2017
Autism typically involves the inability to read social cues. We most often associate this with visual difficulty in interpreting facial expression, but new research at the Weizmann Institute of Science suggests that the sense ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.