Multiple gene mutations linked to autism

In two separate studies, scientists working at Vanderbilt University in Tennessee, US have shown that a faulty gene involved in controlling levels of the brain chemical serotonin is linked to an increased risk of autism.

The first study, published in the American Journal of Human Genetics, shows that many different mutated forms of the serotonin transporter gene (SERT) are associated with the condition. In the second, published online in the Proceedings of the National Academy of Sciences (PNAS), the researchers show how these SERT mutations may disrupt serotonin signalling in autism. The findings could lead to more targeted drug therapies for some children with autism, say the teams.

Autism is a lifelong developmental disability that typically appears during the first three years of life. The disorder affects social and language skills, and the way in which a child relates to people, objects and events. Autism often runs in families, suggesting that it has a genetic basis, although it is thought that the combined effects of at least ten different genes are involved. Previous research has shown that around 25 per cent of people with autism have raised levels of serotonin in their blood - suggesting that this chemical is involved in the disorder. Also, the symptoms of autism improve in some patients treated with selective serotonin reuptake inhibitor (SSRI) drugs such as Prozac, which increase the amount of serotonin available to cells in the brain.

In the latest research, James Sutcliffe and colleagues at the Vanderbilt Center for Molecular Neuroscience followed up earlier work showing a weak link between one version of the SERT gene and autism. They looked at DNA samples from 120 families affected by autism, and identified 19 different SERT gene mutations present in those with more than one affected male. In the second study, Randy Blakely and colleagues at the Vanderbilt Kennedy Center for Research on Human Development showed that the faulty versions of SERT affect serotonin signalling in the brain.

The SERT gene makes a protein whose normal job is to 'vacuum up' excess serotonin in the brain. The PNAS study shows that other brain proteins that fine-tune SERT activity were unable to control five of the ten faulty SERT proteins examined. 'We were stunned because the cell just can't 'talk' to these SERT proteins in the normal way', said Blakely. He added that although it was impossible to extrapolate from a molecule to a person, 'it is striking that these mutations, which do not allow proper communication with SERT, show up in a disorder fraught with communication problems'.

Blakely and Sutcliffe say that the findings could lead to new drug therapies for autism. Sutcliffe adds that it may also be possible to use genetic testing 'to predict which kids would respond positively to particular SSRI medications'. Last week, French researchers also said they were developing a risk assessment test for autism, based on four other genes that affect a person's susceptibility to the condition. The team, from the company IntegraGen SA, aims to launch the test in 2006, and hopes that it will be used to help confirm diagnoses, and also to assess the risk of autism in children too young to show symptoms.