Researchers Find Gene Mutations That May Be a Key to Autism

'Spontaneous' mutations, not generational ones, could play role in up to 20 percent of cases, study says

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By Carina Storrs


HealthDay Reporter WEDNESDAY, April 4 (HealthDay News) -- Genetic mutations that arise spontaneously, as opposed to being passed through generations, could play an important role in the development of autism, new research suggests.

Three research teams sequenced the genes of children with sporadic autism, meaning it did not run in their families, and compared the sequences with those of their parents and siblings. Their results were published in three separate articles on April 4 in the journal Nature.

[Signs Your Child Could Have Autism]

"We found that 15 to 20 percent of sporadic patients could be explained by 'de novo' [or spontaneous] mutations," said Evan Eichler, professor of genome sciences at the University of Washington in Seattle, who led one of the studies.

Overall, the researchers identified hundreds of spontaneous mutations in gene sequences that they predicted would upset the function of the genes in the children with autism. Most of them were only found in single patients.

The good news, according to Eichler, is that the multitude of affected genes seems to belong to just a handful of pathways -- involved in, for example, development or cognition. That suggests that mutations in a diverse set of genes could have a similar biological effect.

"This kind of investigation is of tremendous value for understanding the genetic architecture of risk for autism," said Andy Shih, vice president of scientific affairs at Autism Speaks, a national advocacy group.

"We can probably explain genetic risk factors that might lead to autism in less than 30 percent of the population" from previous research, Shih added.

Autism spectrum disorders, which include both mild and serious forms of autism, affect one in 88 children in the United States, according to just-updated statistics from the U.S. Centers for Disease Control and Prevention.

[CDC: Autism Affects 1 in 88 Children]

The study led by Eichler involved 677 individuals representing 209 different families, each with one child who had sporadic autism. The researchers found a total of 126 spontaneous mutations that they predicted would have a severe effect on the genes in which they occurred.

Eichler's team relied on samples from the Simons Simplex Collection, a nationwide project that gathers blood and DNA from children with sporadic autism and their unaffected family members.

A second study, led by researchers at Yale University in New Haven, Conn., looked at 238 families from the Simons project, some of which overlapped with Eichler's study. They identified 125 de novo mutations that would change the readout of genes among the children with autism and 87 among their unaffected siblings.

The third study in the trio found that just under half of children, both with and without autism, had readout-altering spontaneous mutations, but that the mutation rate was comparable between children with autism and their unaffected siblings. This study was led by researchers at Harvard Medical School, Massachusetts General Hospital in Boston and the Broad Institute in Cambridge, Mass., and involved 175 sets of children with autism and their parents.

Altogether, this body of research suggests that the frequency of de novo mutations is not significantly higher in children with autism, but that the types of mutations, which occur by chance, are more detrimental in children with autism than those in their unaffected siblings, Eichler said.

Eichler's team also found that de novo mutations were four times as likely to lie on DNA strands inherited from the father, and that the number of mutations increases with paternal age.

The possible paternal influence suggests that many of the de novo mutations originate in the father's sex cells, which give rise to sperm. Presumably, mutations would be more likely in paternal sex cells rather than maternal ones because paternal cells continue to divide throughout a man's lifetime, giving them more chances to pick up mutations.

Although the link with paternal age jives with some epidemiological studies that have found higher rates of autism among children of older parents, it probably only plays a part in a modest 10 percent or so of patients, Eichler said.