Contributing gene finally found

USA Today (Society for the Advancement of Education), Feb, 2005

Scientific research has discovered that a specific gene contributes to autism and that autistic people have fewer receptors for the brain messenger acetylcholine, as well as more tightly packed columns of neurons in the cerebral cortex. Another study found that autistic children were less able to discriminate similar sounds than were other youngsters. The research is providing new clues to the genetic, neurological, and molecular basis of this still mysterious disease.

Autism is a disorder that affects two to six of every 1,000 children--mostly boys. It actually encompasses a wide array of symptoms--called autism spectrum disorder (ASD)--including various degrees of behavioral, developmental, and sensory deficits. Many first became aware of autism with the 1988 movie "Rain Man," starring Dustin Hoffman as a middle-aged autistic savant with tremendous mental capabilities. In reality, only about 10% of autistic people display signs of genius--typically in mathematics, music, or art.

Although autism long has been identified as a genetic disease, the genes that contribute to it have been difficult to track down. Unlike Huntington's disease or Down syndrome, in which a single gene or an entire chromosome is inherited, many gene mutations probably are involved in autism. Now the laboratories of James Millonig and Linda Brzustowicz at the University of Medicine and Dentistry, New Brunswick, N.J., have isolated a specific gene that contributes to ASD.

In searching for the gene, the pair focused on previous research showing that autistic people often have a smaller cerebellum, a separate structure at the back of the brain. "The cerebellum is thought to control many of the functions that are impaired in autistic children, such as language and attention span," Millonig points out.

Their next clue came from studies of mutant mice. Mice with a mutation in the Engrailed 2 (EN2) gene also have a smaller cerebellum. While scientists had not yet pinpointed a gene that causes autism, they had identified a particular region of a chromosome that is inherited by autistic children more often than their nonautistic siblings--a clue that the region contributes to the disease.

Millonig and Brzustowicz realized that this identified region contains the EN2 gene. The EN2 gene encodes a protein called a transcription factor that binds to cells' DNA to control the expression of dozens or even hundreds of other genes. Therefore, a variation in EN2 could have far-reaching effects on brain development and behavior.

These studies reveal important changes in the neurotransmitter systems of autistic brains and the specific regions of the brain in which they occur. Together, this information ultimately may help guide pharmaceutical companies to develop drugs that specifically target the underlying causes of autism and not just the behavioral symptoms.