NAAR-Funded Researchers Announce Finding

UMDNJ Researchers James Millonig & Linda Brzustowicz Investigating Potential Cerebellum-Autism Link

NAAR-funded researcher Dr. James Millonig, of the University of Medicine and Dentistry of New Jersey (UMDNJ) in Piscataway, NJ, released information today at the American Society for Human Genetics meeting in Los Angeles about his study that suggests the gene ENGRAILED 2 is possibly linked to autism.

Dr. Millonig received a two-year, $120,000 award in 2003 for his project, "Studying Mouse Cerebellar Development as a Tool to Identify Autism Susceptibility Genes," which is related to his work on the ENGRAILED 2 gene. Dr. Millonig is working on this project with another NAAR-funded researcher at UMDNJ, Dr. Linda Brzustowicz, who recently leveraged data from her pilot study funded by NAAR in 2000 into a larger award from the National Institute of Mental Health.

Interestingly, the ENGRAILED 2 gene is also being studied by another of NAAR's 2003 award recipients: Dr. Karl Herrup, of Case Western Reserve University in Cleveland, OH. NAAR awarded Dr. Herrup a two-year, $120,000 award for his project, "The ENGRAILED 2 Mutant as a Model for the Neuropathology of Autism."

Science magazine reported on Dr. Millonig's announcement at the American Society for Human Genetics meeting in today's edition. The story is listed below.

From Science Magazine

Gene Variant Linked to Autism

Geneticists have found strong evidence implicating a developmental gene in autism, they announced today at the annual meeting of the American Society of Human Genetics in Los Angeles. Although it's not known what the variant of the gene does, the finding backs the idea that something goes wrong with the developing brain.

“This is a truly exciting finding,” says Eric Courchesne of the University of California, San Diego. “If replicated, this could lead to some very novel approaches to early detection.”

Because symptoms often start to appear at 2 years of age or so, parents have blamed childhood vaccines received at that age. Scientists have learned, however, that something is unusual about these children even before diagnosis.

Courchesne, for example, has shown that the autistic brain is already strikingly abnormal by the first months of life. Children with autism usually have an abnormal cerebellum, a region that participates in many processes that go awry in autism, such as the ability to control attention.

The cerebellum-autism link intrigued Jim Millonig, a mouse geneticist at the University of Medicine and Dentistry of New Jersey in Piscataway. He knew that in mice, a gene called ENGRAILED 2 is involved in development of the cerebellum. Moreover, in humans the gene is located on a chromosomal region called 7q, which other studies have linked to autism.

Millonig teamed with Linda Brzustowicz of Rutgers University and colleagues to look for gene variations in a data set called the Autism Genetic Resource Exchange (AGRE). After examining 167 families with at least two children with autism, they found that autistic children were twice as likely to have inherited a particular form of the ENGRAILED 2 gene than were children without autism.

“It's so statistically significant in this population that it's not going to go away,” Millonig says.

It's not yet clear that ENGRAILED 2 itself is hiking the risk of autism, Millonig cautions, but it's a strong clue that a version of the gene or DNA near it is involved. The team is now trying to replicate the finding in a data set of 365 families.

“It's a really strong candidate,” says autism geneticist Margaret Perivak-Vance of Duke University Medical Center in Durham, North Carolina. But she cautions that many candidate genes have failed to be replicated. (A study published earlier this year found no association between ENGRAILED 2 and autism.) In addition, autism is likely caused by anywhere from two to 10 genes.

Millonig agrees. “This is just one bit of the whole puzzle,” he says.