On March 29, 2012, the US Centers for Disease Control reported startling evidence: the number of children diagnosed with autism in the United States increased 25% between 2006 and 2008. The autism rate jumped from 1 in 100 (2006) to 1 in 88 children (2008). The autism rate is even higher for boys: one in 54 compared to girls, one in 252.
This CDC report was featured as headline news throughout the media–but not The New York Times, which buried the CDC news report on page A20.
Yesterday, The Times published on its front page an article under the headline, "Scientists Link Gene Mutation To Autism Risk," reporting that three teams of scientists found several rare spontaneous gene mutations in a few individuals with autism whose father was over age 35. The scientists suspect that such gene mutations may result in a 5 to 20 times higher risk of developing autism.
"The gene mutations are extremely rare and together account for a tiny fraction of autism cases, suggesting that the search for therapies will be a long one, and that what is loosely known as autism may represent a broad category of related but biologically distinct conditions. There are likely hundreds, perhaps thousands, of rare mutations that could disrupt brain development enough to result in social and developmental delays."
If rare gene mutations are suspected to be the cause of 5% to, at most, 20% autism, it leaves the most important questions unanswered:
What about the cause of autism in 80% (possibly 95%) of autistic children unanswered?
To date, only the MMR vaccine and mercury in vaccines have been studied.
With so many millions of children affected by autism–and the spiraling increase in that number–shouldn’t scientists take seriously the eye witness reports by thousands of parents who blame vaccines for triggering autistic spectrum in their previously healthy children?
There is a pressing need to examine without prejudice whether the vaccine-autism association is valid by comparing autism (and other health) outcomes in vaccinated vs. unvaccinated children.
Why is such an obviously necessary research approach so contentious and, therefore, neglected?
Whose financial investments are threatened by an analysis of data comparing the health of children vaccinated with those not vaccinated?
THE NEW YORK TIMES
Teams of scientists working independently have for the first time identified several gene mutations that they agree sharply increase the chances that a child will develop autism. They have found further evidence that the risk increases with the age of the parents, particularly in fathers over age 35.
The gene mutations are extremely rare and together account for a tiny fraction of autism cases — in these studies, only a handful of children. Experts said the new research gave scientists something they had not had: a clear strategy for building some understanding of the disease’s biological basis.
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 syndrome and 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.
The new research — reported in three papers posted online on Wednesday in the journal Nature — provides some measure of both, some experts said. 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 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 one 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.
But a team led by Evan E. Eichler, a professor of genome sciences at the University of Washington in Seattle, independently found the same thing in a study of 209 families: one child with autism — and a glitch in the very same gene.
The researchers added still another gene, finding two unrelated children with autism in their own sample who had de novo mutations in the same location. No such coincidences occurred among people in the studies who did not have an autism diagnosis.
Finally — in the third paper — a team led by Mark J. Daly of Harvard ran its own analysis of these three genes, among others, and found yet more cases.
Everyone typically has at least one de novo mutation, Dr. Daly said, but his study suggested that “kids with autism have a slightly higher rate, on average, and the effects are more severe.”
All three studies also found evidence that the risk of de novo mutations increases with parental age. In an analysis of 51 de novo mutations, Dr. Eichler’s group found that glitches were four times more likely to originate in DNA from the male than from the female. The risk is higher in fathers at 35 than at 25 and seems to creep up with age. This offers one possible explanation for earlier research linking older fathers with autism’s rise: older male sperm is more subject to small, perhaps random glitches that in rare cases affect brain development.
The emerging picture suggests that the search for therapies will probably be a very long one, and that what is known generally as autism may represent a broad category of related but biologically distinct conditions. But both Dr. Eichler’s and Dr. Daly’s groups found some evidence that high-risk genes interact in shared biological processes.
“This is really the tip of the tip of the iceberg,” Dr. Eichler said, “but I think the important thing is all of us agree on where to start.”
Dr. State added, “From my standpoint, this is a big deal, because I’ve been at this a long time, and for years and years you couldn’t get anyone to believe you’d even found one gene” that significantly increased risk.
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