New research points to genetic stratification of autism

7 July 2014

Research led by Seattle Children’s Autism Centre has identified a genetic mutation associated with a specific form of autism.

An international collaborative study of more than 6,000 children with autism spectrum disorder (ASD) and more than 8,700 healthy controls identified fifteen who shared both definitive diagnoses of ASD, similar symptoms (including sleep and gastrointestinal problems) and facial features, along with a mutation in the CHD8 gene.

The researchers found that disruption of the CHD8 gene in the zebrafish caused equivalent facial abnormalities and signs of impaired digestion, lending weight to their conclusion that mutations in the gene were responsible for both autism and the other characteristic features.

Describing the finding as a ‘game changer’ for research, Clinical Director and lead researcher Dr Raphael Bernier observed: “It’s possible we may be able to look at features in utero and determine a higher risk of autism, possibly even early detection”. It was suggested that a combination of genetic testing and identification of the abnormal facial features via ultrasound could identify fetuses at high risk of this form of autism. Although there is no cure, early identification and treatment of the disease (ideally from as early as three months) can improve outcomes significantly.

However, any form of prenatal testing or screening would need very careful consideration of the potential risks and benefits; not only does ASD vary considerably in severity, but it is known to have environmental influences as well as genetic ones so that in general terms, prenatal genetic testing would only reveal risk rather than provide diagnosis – a dilemma for parents and clinicians alike.

The CDH8 mutations appear to be unusual in having both strong penetrance (likelihood of causing symptomatic disease) and associated physical features, making it more appropriate for testing, but only a very small minority of ASD cases are likely to be caused by these particular mutations. Dr Bernier has cautioned that “Children with autism are incredibly diverse so we must determine the genetic causes of different subtypes to find effective treatments”; this would also apply to testing.

In this case, the authors of the new research go so far as to suggest that genetic insights such as this underline the potential for eventual stratification of the ASD patient population into new categories or sub-groups. This could not only aid diagnosis and clinical management, but also provide the basis for corresponding stratification in drug trials.

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