Their next clue came from studies of mutant mice. Mice with a mutation in the ENGRAILED 2 (EN2) gene also have a smaller cerebellum. And 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.
In earlier work, Millonig and his colleagues found two heritable variations in the DNA sequence of the EN2 gene. "These specific variations were twice as likely to be inherited by autistic siblings," says Millonig. In the original study, published in the May 2004 issue of Molecular Psychiatry , the group tested the DNA of 167 families with autism. They have now repeated those tests in an additional 381 families. The evidence from the total of 548 families strengthens the case for EN2 as an autism 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.
The next step in this line of research will be to show that the variations in EN2 have an effect on the transcription factor's function. "We hope that by identifying this and other genes involved in autism, we will be able to detect individuals at high risk for autism and use early interventions to lessen the symptoms as they develop," Millonig says.
In other research, Gene Blatt, PhD, and his colleagues at the Boston University School of Medicine found that a specific type of receptor for the neurotransmitter acetylcholine was expressed at lower levels in a specific brain area of autistic people compare
Contact: Leah Ariniello
Society for Neuroscience