CSHL Scientists Confirm Genetic Distinction Between Heritable and Sporadic Cases of Autism

Science Publishes "Strong association of de novo copy number variation with autism"

Autism is thought to be the most highly heritable of all neuro-psychiatric disorders. Yet, most cases of this childhood developmental disorder that severely affects social interaction and communication are “sporadic” and come with no family history. New research, led by Cold Spring Harbor Laboratory (CSHL) scientists Jonathan Sebat, Lakshmi Muthuswamy and Michael Wigler, has found a distinction between heritable and sporadic forms of the disease. These findings may influence future autism research and diagnostic testing.

“We found that many children with autism have spontaneous mutations in their DNA.  This occurs more often in the sporadic cases than in either familial cases or in healthy children,” said Sebat. The study, published in the March 16, 2007 edition of Science, reports that at least 10% of children with autism carry an alteration in their DNA that is not found in either parent, a much higher rate than is observed in healthy children.  To date, most genetic studies of autism have focused on families with multiple autistic children. “Our findings suggest that sporadic autism is genetically distinct from the type that runs in families, and that we must use different approaches for studying them,” concluded Sebat.

“Sporadic autism is the more common form of the disease, and even the inherited form might derive from a mutation that occurred in a parent or grandparent,” explained Wigler. Using a high-resolution method for analyzing DNA called microarray technology, the researchers found that spontaneous copy number mutations occur primarily in sporadic cases. The study reports that these new mutations were found less frequently in families that have more than one child with autism.

The results strengthen the scientific basis for using microarray technology for diagnostic testing. Methods for detecting spontaneous mutations will provide important information for children with autism and their parents. This information could help to determine the risk of having a second child with autism, and the knowledge of which genes are involved may lead to the development of new therapies.

“This work received the vast bulk of its funding from the Simons Foundation, which generously supported the research when it was little more than an idea and a technique,” Wigler acknowledged.  In addition to the Simons Foundation, other supporters of this research included The National Institute of Mental Health, Autism Speaks, Cure Autism Now, and the Southwestern Autism Research and Resource Center.

“This discovery sets a new framework for understanding, diagnosing and potentially treating autism,” said CSHL President Bruce Stillman. CSHL is pursuing a $200 million capital campaign that will include construction of new research facilities dedicated to the study of autism.

The full citation of the paper:

C. Sebat et al., Science, 15 March 2007 (10.1126/science.113569). To access the publication on line go to:

http://www.sciencemag.org/cgi/content/short/1128659

CSHL is a private, non-profit research and education institution dedicated to exploring molecular biology and genetics in order to advance the understanding and ability to diagnose and treat cancers, neurological diseases, and other causes of human suffering.  For more information, visit www.cshl.edu.