Houston scientists and their colleagues have proposed a new explanation for what causes autism, a neurological disorder that affects about one in 1,000 children.
While many researchers believe inheritance of faulty genes is at autism's root, the new idea suggests that the cause is more complex. Errors in genes may combine with so-called "epigenetic" errors, and either may be inherited or occur for the first time in the affected child, says Dr. Art Beaudet, a geneticist at Baylor College of Medicine. Epigenetic errors cause cells to use genes abnormally, but are distinct from errors in genes themselves.
An article describing the new theory appeared online last week in the American Journal of Medical Genetics Part A. Dr. Huda Zoghbi, also a geneticist at Baylor, said the proposal offers a fresh idea to researchers still struggling to figure out what causes autism, even after many years of research.
"I think Art's model is the most efficient," says Dr. Zoghbi, who is also a researcher with the Howard Hughes Medical Institute. "It reconciles all the issues. He really thought about all these different scenarios and pulled them together to come up with a solid hypothesis to explain autism."
Autism has many variations, but it typically begins in childhood. It can impair thinking, language and the ability to relate to others. Boys with autism outnumber girls by a ratio of more than 3-1. And in recent years, for reasons that are still unclear, the number of reported cases of autism has skyrocketed.
Researchers have focused on finding a genetic cause for the disorder because autism runs in families. For instance, if one identical twin has autism, the other twin's chance of having autistic symptoms are as high as 90 percent. Fraternal twins and siblings are also at increased risk if a brother or sister has the disorder.
"So one argument has been," Dr. Beaudet says, "that there are many genes involved "maybe 10 or 15 or 20" and that some magical combination causes autism."
But there are other hints about how autism occurs. In rare cases, children develop autism when they inherit a faulty gene from one parent, but not when they inherit it from the other. This is the hallmark of an "epigenetic" effect, a modification to genetic information that changes how the gene is used but does not affect the makeup of the gene itself. Epigenetics is a relatively new frontier in biomedical research, and scientists are just beginning to look for epigenetic links to disease.
Dr. Beaudet says he hopes scientists will have more success at finding the cause of the vast majority of autism cases by broadening their search for clues. In addition to considering epigenetic "instead of only genetic" effects, Dr. Beaudet says scientists should look beyond inherited causes.
Genetic or epigenetic errors could pop up for the first time in each patient individually, instead of being inherited from parents. The medical community already knows of genetic disorders that occur for the fist time in a new generation. A classic example is Down syndrome, a mental retardation condition caused by an extra chromosome.
If autism is really popping up new in most children, Dr. Beaudet says, it could explain why the many large studies that focus on genes passed from parents to children haven't found culprit genes for the majority of cases.
In the new study, Dr. Beaudet proposes that problems with a gene linked to a neurological condition called Angelman syndrome also may cause autism. Dr. Beaudet and his colleagues found epigenetic changes to that gene in the brain of a patient with autistic features. Examination of many other brains of autism patients, however, didn't show the same change.
Data to support Dr. Beaudet's theory are scarce at this point, he says. He concedes that the whole idea may even be wrong. But at present, he contends, the theory fits with everything scientists know about autism, and deserves further study.
His own studies, he says, will focus on the UBE3A gene and others in mice. One theory he'd like to test is whether nutrients such as folic acid can result in epigenetic changes to genes linked to autism. Other studies have shown that nutritional supplements that include folic acid cause epigenetic alterations of other genes. And, he says, an increase in dietary folic acid "from prenatal vitamins and fortification of the food supply" has overlapped the increase in cases of autism.
It's pure speculation at this point, Dr. Beaudet says, but "in my mind there's a potential connection."