Teams of scientists working independently to understand the biology of autism have for the first time homed in on several gene mutations that they agree sharply increase the chances that a child will develop the disorder, and have found further evidence that the risk increases with the age of the parents, particularly in fathers over age 35.
Evan McGlinn for The New York Times
Dr. Matthew W. State, a professor of genetics and child psychiatry at Yale led a team that looked for de novo mutations in 200 people who had been given an autism diagnosis.
Diagnoses of Autism on the Rise, Report Says (March 30, 2012)
Evan McGlinn for The New York Times
A team led by Mark J. Daly of Harvard, above, found that the rate of de novo mutations was slightly higher among 175 people with a diagnosis of autism than in the general population.
Share your thoughts.
The gene mutations are extremely rare and together account for a tiny fraction of autism cases — in these studies, only a handful of children. But the odds that two or more people in any small group will have such problems in the same genetic location are vanishingly small, strongly suggesting that the mutations are related to the diagnosis.
Scientists have been debating the relative influence of inherited risk and environmental factors in autism for decades, and few today doubt that there is a strong genetic component. But biologists have groped in vain for a reliable way to clarify the underlying genetics of these so-called autism spectrum disorders, including Asperger syndromeand related social difficulties that are being diagnosed at alarmingly high rates — on average, in one in 88 children, according to a government estimate released last week. Previous studies have produced a scattering of gene findings but little consensus or confidence in how to proceed.
Experts said the new research, reported in three papers published online Wednesday in the journal Nature, provides a measure of both, giving scientists something they have not had: a clear strategy for building an understanding of the disease’s biological basis. There are probably hundreds, perhaps more than a thousand, gene variations that could disrupt brain development enough to result in social delays. An intensified search for rare mutations could turn up enough of these to account for 15 percent to 20 percent of all autism cases, some experts say, and allow researchers a chance to see patterns and some possible mechanisms to explain what goes awry.
“These studies aren’t so much a breakthrough, because we knew this was coming,” said Jonathan Sebat, a professor of psychiatry and cellular and molecular medicine at the University of California, San Diego, who was not a part of the research teams. “But I’d say it’s a turning point. We now have a reliable way forward, and I think it’s fair to expect that we will find 20, 30, maybe more such mutations in the next year or two.”
Other researchers were more cautious, saying that the genetics of rare mutations was not yet well enough understood to make conclusive statements about their effect on the behavior of specific genes.
“This is a great beginning, and I’m impressed with the work, but we don’t know the cause of these rare mutations, or even their levels in the general population,” said Dr. Aravinda Chakravarti, of the Institute of Genetic Medicine at the Johns Hopkins University Medical School, who was not involved in the studies. “I’m not saying it’s not worth it to follow up these findings, but I am saying it’s going to be a hard slog.”
The three research teams took a similar approach, analyzing genetic material taken from blood samples of families in which parents who have no signs of autism give birth to a child who develops the disorder. This approach gives scientists the opportunity to spot the initial mutations that accompany the condition, rather than trying to work though possible genetic contributions from maternal and paternal lines. In all three studies, the researchers focused on rare genetic glitches called de novo mutations.
De novo mutations are not inherited but occur spontaneously near or during conception. Most people have at least one, and the majority of them are harmless.
In one of the new studies, Dr. Matthew W. State, a professor of genetics and child psychiatry at Yale led a team that looked for de novo mutations in 200 people who had been given an autism diagnosis, as well as in parents and siblings who showed no signs of the disorder. The team found that two unrelated children with autism in the study had de novo mutations in the same gene — and nothing similar in those without a diagnosis.
“That is like throwing a dart at a dart board with 21,000 spots and hitting the same once twice,” Dr. State said. “The chances that this gene is related to autism risk is something like 99.9999 percent.”
The team found that a third child had a de novo mutation in another gene suspected of a possible link to autism risk — but one such mutation is not enough to make the case.