A study published today in the journal Nature is a significant step toward understanding the genetic causes of autism. It identifies seven new genes that are almost certainly linked to autism and 20 more that have at least a 90 percent chance of being true autism genes. Doctors could potentially test for these genes before birth.
The study also identifies several hundred more gene mutations found in autistic children but not in their siblings. These mutations have about a 50/50 chance of playing a role in the condition.
The researchers, who came from several top universities and research centers, aren’t the first to flag genes as possibly or even probably linked to autism. But the specific genes they point to shed light on both the biology and the epidemiology of a disorder that has remained mysterious, even as diagnosis rates have more than doubled since 2000.
‘High-IQ’ Versus ‘Low-IQ’ Autism
Scientists analyzed exomes, or sections of DNA that code for proteins, from more than 2,500 autism patients and their unaffected siblings. They found that de novo gene mutations, or those that occurred spontaneously during development, accounted for more than a quarter of the autism cases.
“This is like lighting a candle in a dark, dark room,” said Evan Eichler, a University of Washington geneticist and one of the paper’s authors. “These are the best genes that we have in the history of this disease in terms of being relevant.”
The findings reveal that higher-functioning autism and lower-functioning autism have different genetic origins and may require different interventions.
Another of the study’s authors, Michael Ronemus, a researcher at Cold Spring Harbor Laboratory, said that finding was the opposite of what he had expected.
“We thought we’d see severe mutations that cause the severe cases. We didn’t really find black and white evidence, it’s more gray,” he said.
Higher-functioning autism — which popular media portrays as savant-type behavior — affects boys almost exclusively. The more crippling “low-IQ” form sometimes affects girls.
The gene mutations in the girls in the study were the most severe, suggesting that girls may be protected against the effects of the smaller mutations, particularly later in their fetal development.
Since the research sheds more light on the causes of debilitating “low-IQ” autism, it will make these cases easier to diagnose.
“For individuals with high-IQ autism, we’re still in the dark about what’s causing it,” Eichler said.
Research Paves the Way for Autism DNA Test
The genetic findings are strong enough that if a child with developmental trouble also had one the most clearly implicated genes, doctors could route the child into the best available therapy right away.
“I don’t think anybody could argue that that wouldn’t be a good outcome,” Ronemus said.
It’s also easy to see how these findings might lead to a prenatal test to tell parents the chances that their child will have autism.
The ultimate aim is to find the physical and neurological drivers of autism. This research may open the door to new biological findings as well, since the mutated genes found in the autistic children cluster around particular developmental processes.
“There seems to be a molecular logic, if that’s the right word, in terms of the pathways that are being hit. It’s not just willy-nilly all over the place. It’s a subset of genes related to a common biology,” Eichler said.
For instance, the affected genes also play a role in intellectual disability, schizophrenia, and fragile X syndrome, a rare genetic defect that many suspect is linked to autism.
Working forward from their gene mutations, researchers may be able to pinpoint the abnormal developmental processes at work in all these conditions — and find a way to fix them.
“That’s the real hope of this work,” Ronemus said.