TORONTO - A gene mutation found in some people with autism appears to disrupt very early stages of brain development and contribute to the nervous system deficits that are the hallmarks of autism disorder, a York University study has found.

The study traces the link from autism and a mutated gene to the molecular mechanisms of cell signaling that occur as the brain is developing. It provides the first direct evidence that this gene influences brain development and the incidence of autistic behaviour.

Modern imaging equipment and molecular neuroscience techniques enabled the researchers to show how the protein encoded by this gene controls normal cell function and how this fails when the gene is mutated in individuals with autism.

“If we can identify defects in genes or molecules and the signaling pathways early in brain development – as we have in this study – then it should be possible to develop more effective treatments for children within three years of age, which is when autism is diagnosed,” said Dorota Crawford, an assistant professor of Kinesiology and Health Science in the Faculty of Health at York.

The study, entitled “The E646D-ATP13A4 Mutation Associated with Autism Reveals a Defect in Calcium Regulation,” is published online in the journal Cellular and Molecular Neurobiology. It represents a critical step toward the eventual development of pharmaceutical treatments for children affected with autism. It will also be of interest to scientists who are studying the same family of proteins, which are involved in other neurological diseases such as Parkinson’s disease.

Crawford found the gene mutation in a 2005 study of individuals with Autism Spectrum Disorders (ASD), which are characterized by lifelong impairment in communication and social interaction, coupled with repetitive behaviour, and affect about 190,000 Canadians. That study, in which blood samples were examined for their genetic content, revealed an unknown gene that was mutated in about 20 per cent of the autistic individuals tested – a genetic marker for autism.

In the current study, Crawford, working with former York undergraduate student Janaki Vallipuram, who is first author on the paper, and York graduate student Jeffrey Grenville, characterized the biological function of the protein in the mutated gene. They determined that it is involved in calcium signaling, which is critical for the development of neurons, and then showed that the mutation may contribute to neuronal deficits in the brain and autism.

Crawford is on the faculty of York’s growing Neuroscience Diploma Program and is a member of the York Autism Alliance, a new research group whose interdisciplinary approach includes clinical, behavioural and neurophysiological experiments. Researchers in Crawford’s molecular neuroscience laboratory at York are examining how genetic, molecular and cellular neurobiology and environmental factors contribute to the brain development of children with autism. The recently-completed study is the first to use a state-of-the-art microscope imaging system funded by the Canada Foundation for Innovation and Ontario Research Fund, which was essential because it allowed researchers to take images of living neuronal cells. The study was also supported by the Natural Sciences and Engineering Research Council (NSERC) of Canada.