Harvard Medicine

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A Telling Signature

Researchers at Boston Children’s Hospital have developed a blood test for autism spectrum disorders that outperforms existing genetic tests. The test, described December 5, 2012, in PLoS ONE and based on the largest gene-chip investigation ever done in autism, could enable early diagnosis of autism in about two-thirds of patients before clear symptoms start to appear. In the United States, the average age of diagnosis is five years.

A research team led by Sek Won Kong of the Boston Children’s Hospital Informatics Program looked for differences in gene expression in RNA in blood samples from 66 male patients with autism spectrum disorders and compared them with 33 age-matched males without a disease spectrum disorder.

“Since brain biopsy isn’t a viable option for research, we asked whether blood could serve as a proxy for gene expression in the brain,” says Isaac Kohane, director of the program and senior investigator on the study. “We found that it could.”

In their analysis of the blood samples, Kong and colleagues first flagged nearly 500 genes as having distinct expression patterns in the autism spectrum disorder group, then narrowed that group to 55 genes that correctly identified or ruled out autism in 76 percent of samples.

The gene signature approach, which Children’s has licensed for development, can potentially diagnose autism far more often than the genetic tests currently available. Those tests look for a variety of autism-related mutations—from small “spelling” changes, to lost or extra copies of a gene or genes, to wholesale chromosome abnormalities. Taken together, however, the known mutations account for fewer than 20 percent of autism cases.

“By looking at this fifty-five–gene signature,” says Kohane, “we can say with about seventy percent accuracy that ‘this child does not have autism,’ or ‘this child could be at risk,’ putting the child at the head of the queue for early intervention and evaluation. And we can do it relatively inexpensively and quickly.”