Genetics and stem cells

'Autism gene discovered' by researchers

“Genetic mutation discovered in people with autism,” The Daily Telegraph reports.

The newspaper goes on to say that this mutation “cuts communication between brain cells to about one-tenth of normal levels” and offers “a likely explanation” for the cognitive and behavioural difficulties experienced by people with autism.
This headline is loosely based on recent research into the impact of a previously discovered genetic mutation on the ability of brain cells to transmit signals. The Telegraph speculated that misfiring signals could cause the symptoms of autism.

The study was conducted using rat brain cells, and did not involve people with autism directly.

The researchers described the detailed molecular processes that occur between brain cells when the level of a specific protein is changed. Previous research had discovered that mutations to the gene that controls this protein occurred in people with some types of autism. The authors found that varying the level of this protein affected other proteins responsible for communication between the rats’ brain cells.

The research did not, however, examine the impact of this disrupted communication in people with autism, and should not be interpreted as offering “a likely explanation for their cognitive and behavioural difficulties” as reported by the Telegraph.

In addition, many experts think that autism may arise as the result of a combination of factors – not just genetics. Viewing autism as a purely genetic disease may well be an over-simplification.

Where did the story come from?

The study was carried out by researchers from Stanford University, the University of Auckland and Ulm University in Germany. The research was funded by the National Institute of Neurological Disorders, the US National Institutes of Health and other organisations throughout the US, New Zealand and Germany.

The study was published in the peer-reviewed Journal of Neuroscience.

While the Telegraph appropriately pointed out that a treatment based on this research is years away, their coverage of the study is flawed. To start with, this research did not discover a genetic mutation in people with autism. That link had been previously established. The Telegraph’s coverage also fails to mention that the study was conducted in rats, and further misguides readers by picturing a scan of a human brain.

What kind of research was this?

Autism is often referred to by clinicians as Autistic Spectrum Disorders (ASDs) as there is a spectrum of autistic-type symptoms that, while sharing common features, can also vary considerably between individual cases.

This was a laboratory study that examined the impact of a genetic mutation on signalling (neural pathways) between rats’ brain cells.

Previous studies have linked several different genes to autism. This study looked specifically at one gene that contains the information used to make a protein called ProSAP2/Shank3.

People who lack one copy of this gene have a syndrome called Phelan McDermid syndrome – a syndrome with autism-like features. Other mutations in this gene have also been associated with autism.

Having three copies of the ProSAP2/Shank3 gene (rather than the usual two copies) has been associated with Asperger syndrome. This is a form of ASD that is usually associated with unaffected language development skills, but problems with social interaction and behaviour. While spoken language is unaffected in most people with Asperger syndrome, they often have difficulty understanding figures of speech (such as “it’s raining cats and dogs”).

The authors say that while the ProSAP2/Shank3 mutation has been linked to ASDs, scientists have not identified the specific functions of the protein that could account for this relationship. This study sought to characterise the protein’s function in sending signals between brain cells.

What did the research involve?

The researchers report that mutations in multiple genes have been linked to ASDs, and many of these affect proteins found in the part of nerve cells that make contact with other nerve cells and transmit signals. These connections within the nervous system are referred to as synapses.

Previous research on genetic mutations linked to ASDs suggests that these mutations may affect the synapses and how the nerve cells send signals and communicate with each other.

This study looked at how the ProSAP2/Shank3 protein affects other proteins at the synapse and how the nerve cells signal to each other. The researchers used rat brain cells grown in the laboratory and used various different methods to study the protein.

What were the basic results?

The researchers found that the levels of the ProSAP2/Shank3 protein affect the levels of other proteins at the synapse that are important in nerve cell signalling, and influence how signals are transmitted between nerve cells.

When the researchers looked at the mutated forms of ProSAP2/Shank3 that are associated with ASDs, they found that these abnormal forms of the protein disrupt nerve cell signalling.

How did the researchers interpret the results?

The researchers concluded that mutations to the ProSAP2/Shank3 gene affect a major brain cell signalling pathway. They say that: “it will be of considerable interest to determine whether other ASD-associated mutations also converge in this pathway”.


This study provides a target for future research into autistic spectrum disorders. The researchers have characterised the role that one protein plays in the signalling process of certain brain cells. But whether this research ultimately leads to the development of treatments for ASDs remains to be seen.

Even if further research reveals that the mutations to the ProSAP2/Shank3 protein play a causative role in autism, it is unlikely to account for or lead to a treatment for all ASDs. The various types of ASD suggest a complex origin of the disorders and a mutation to a single gene is unlikely to account for all the different disorders on the spectrum. There may also be environmental factors involved.

The authors say that as the number of genes found to be linked to ASDs continues to grow, the scientific community faces the challenge of explaining how mutations in so many genes could influence the development of ASDs. They suggest that multiple genetic mutations may affect the signalling pathway characterised in this study, and that further research that focuses on this pathway may be useful.

This study explored the effect of a genetic mutation on a specific signalling pathway in the brain that may be involved in some forms of autism. Contrary to the news headlines it did not discover a genetic mutation in people with autism and should not be interpreted to explain any cognitive or behavioural symptoms associated with autism or autistic spectrum disorders.

A greater understanding of the genetics and biology of ASD may eventually lead to new treatment options, but as the lead researcher is quoted as saying in The Daily Telegraph story, such treatments are likely to be years away.

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