Single Gene Mutation Doubles Autism Risk

A single gene mutation doubles a child's susceptibility to autism, a Vanderbilt-led research team reports.

It's a discovery with far-reaching implications. Why? It isn't specifically a brain gene. In fact, it affects multiple systems in the body, including immune function and gut repair. The gene in question is a variant form of a gene called MET.

This suggests that the complex set of behaviors and mental disabilities we call autism may not, as previously thought, be solely a problem with brain development. It may also be linked to subtle developmental problems throughout the body.

The study, which included Pat Levitt, PhD, of the Vanderbilt Kennedy Center for Research on Human Development, appears in the early online edition of the Proceedings of the National Academy of Sciences.

"We hypothesize that the common, functionally disruptive [MET gene variant] can, together with other vulnerability genes and [genetic] and environmental factors, precipitate the onset of autism," Levitt and colleagues suggest.

What Raises a Baby's Risk of Autism?

Early Signs of Autism Identified in Infants

New Autism Gene Important

Kids with autism usually seem normal at first. Then they seem to backslide, losing abilities they once had and suddenly withdrawing into their own world.

There are many theories about why this happens. Clearly, something goes wrong with normal development.

The MET gene, Levitt and colleagues note, encodes an important enzyme called the MET receptor. Among other things, the MET receptor sends out signals important for brain growth, brain maturation, immune function, and gut repair.

Many parents of children with autism report that their kids have digestive problems and haywire immune responses. It's never been clear whether this is directly or indirectly linked to their autism.

Linking the MET gene to autism opens the door to exciting new research, notes Matthew W. State, MD, PhD, director of the neurogenetics program at Yale University. State's editorial accompanies the Levitt team's report.

"The possibility that a MET variant might lead to immune dysfunction and gastrointestinal disturbance along with autism-spectrum disorders is an important question to pursue and one that will likely lead to some debate," State writes.

That's because the first theory to link autism, gut problems, and immune dysfunction blamed these symptoms on childhood immunization with the measles/mumps/rubella (MMR) vaccine.

That theory -- now rejected by all but one of the researchers who first proposed it -- holds that kids who develop autism are particularly sensitive to the toxic effects of thimerosol, a form of mercury used as a vaccine preservative.

The thimerosol theory was rejected by an Institute of Medicine panel of experts. Now the MET gene may reopen investigation into the link between autism and other developmental problems.

"The very important question of whether and how gut disturbance, regression, and immunological issues may be related has been, in part, obscured by this [thimerosol] controversy," State writes. "Hopefully, the present study will lead to additional rigorous investigations of these questions without fueling unnecessary concern regarding MMR."

Older Dads Have More Autistic Kids

Brains of Autistic Kids May Be Bigger

By Daniel J. DeNoon, reviewed by Louise Chang, MD

SOURCES: Campbell, D.B. Proceedings of the National Academy of Sciences, early online edition, Oct. 16-20, 2006. State, M.W. Proceedings of the National Academy of Sciences, early online edition, Oct. 16-20, 2006.