A blog about resources for autism and care and treatment.

Thursday, April 5, 2012

Scientists Link Gene Mutation to Autism Risk

By 
New York Times

Kevin P. Casey for 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 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 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 Dr. 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.
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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.

Finding Some Zen

Guest Blogger
Nicole Lindstrom

Rushing around is something that is common for people with children. It is even more common for families with children that have special needs/autism. Last week between my drop off at school and on to one of our therapy appointments, I had a moment to escape to yoga.

I am lucky enough to be able to practice yoga once or twice a week due to my husband’s availability at home. Yoga has been something that I viewed as a stress relief but now to me it has become a need and a way of life. During one of these classes, my yoga instructor ended our class with a spritz of lemon grass green tea spray while we were relaxing in our corpse pose. She sprayed this spray as she said to “open the mind and the sense."

While lying there, I recalled the week. It had been very hectic to say the least. My son who has been progressing this school year had picked up some frustrating behaviors boarding on obsessive traits with his schoolwork having to be perfect. Mind you in the beginning of the year he could barely color and recognize the lines now he is coloring perfectly but finding going outside the lines was causing meltdowns in the classroom, thus we had to pick up some more help, behavioral therapy. There was my one step back.


The spray that was spritzed over me while lost in my thoughts and search for peace really did open my mind and senses. It was such a beautiful smell. It made me realize when was the last time I wasn’t so lost in my thoughts and worries that I actually used my senses. Really stopped and “smelled the roses”.
As parents and caregivers to these wonderful children we get so focused on our organized day and our to and fro that we have little time to think about our thoughts and our needs.
When was the last time as a parent you truly listened to the words of a song like you did back in high school when you believed some songs were written just for you? Or watched the beauty of the day despite what is going on in your life? I believe a means of good therapy for parents of autistic children should be a need to find a good escape. A place or time in the day where you can find time for your own inner thoughts to just simply be.

After that class, I cried, I cried for no reason at all except for the pure fact that I smelt something like I did for the first time in years. I took a moment to breathe and to focus on the moment at hand. I actually took a moment for myself to recharge and to know that I am doing the best that I can. By doing so, it allowed me to battle the rest of the week with some renewed energy.
What is your escape?