Three independent autism studies have for the first time found several gene mutations, particularly ones from older fathers that significantly increase children’s risk for developing the disorder.
Autism Spectrum Disorder (ASD) has been previously linked to family genetics, but the mutations found in the latest studies suggest that autism can be caused by mutations that are not shared by either parent and occur for the first time in the production of sperm or egg cells.
Researchers conducted exome sequencing, a method that analyzes all the protein coding regions of the human genome, accounting for 23,000 genes but only 2 percent of the entire genome, to find the ‘de-novo’ gene mutations, CHD8, SNC2A and KATNAL2, which cause “sporadic autism” are extremely rare are together account for a small fraction of autism cases.
All together, the three studies, all published online in the journal Nature, consisted of 580 families of children with autism, and suggest that the mutations that occur in the part of the DNA where the proteins are programmed could play a role in the development of autism.
One of the studies conducted by scientists at the University of Washington sequenced the DNA of 209 families with autistic children where the child was the only one in the family with the disorder and found 248 protein altering ‘de novo’ mutations, with 60 identified as the most likely to raise the risk of autism.
University of Washington researchers also confirmed older findings that older men were more likely to have autistic children, and compared to eggs, sperm had a four times greater effect on the development of autism. The study found that risk of these mutations leading to the onset of autism in children began to increase for fathers as early as 35 years of age.
The second study from Harvard University focused on three new genes that had been linked to the developmental disorder, and the third study from Yale focused on how the different de novo mutations found in autistic patients disrupted the genes that have been linked to brain development, but not to those without a diagnosis.
Using exome sequencing, experts believe that they may be able to identify 200 mutations linking to autism spectrum disorders within three years, in addition to the 100 genes that have already been found.
Scientists say that there are probably hundreds if not thousands of rare mutations that could disrupt brain development to result in social and developmental delays, which all represent an expansive category of related but biologically different conditions known as autism.
"Autism, like many heritable disorders, results from the action of many genes — not simply a single gene as in cystic fibrosis or Huntington's disease," Mark Daly of Harvard, lead author of the study that found that the rate of de novo mutations was higher among the 175 people diagnosed with autism compared to the general population, said in a statement. "These genes hold key insights into the true biological causes of autism — insights we have been unable to gain through other lines of research."
Experts not involved in the study say that the latest findings confirmed that while many these genetic mistakes that occur across the genetic code are harmless, they can also cause substantial problems when they occur in parts of the genome needed for brain development, resulting in a five to 20 times greater chance of developing autism.
"These results confirm that it's not the size of the genetic anomaly that confers risk, but its location," said Dr. Thomas Insel, director of the National Institute of Mental Health, one of the National Institutes of Health, which funded one of the studies.
“These results clearly demonstrate the potential of DNA sequencing technology to articulate specific risk factors for autism,” Daly added. “We have only scratched the surface but, with continued collaborative efforts, these gene discoveries will point us towards the underlying biological roots of autism.”
One in 88 U.S. children have autism spectrum disorders, according to the latest report by the U.S. Centers for Disease Control released last Thursday, an overall increase of 25 percent since the government’s last analysis in 2006.
The CDC estimates that about one in 45 boys and one in 252 girls are on the autism spectrum disorder, and it is likely that the developmental condition affects roughly 1 million U.S. children and teens.
Autism, a developmental disorder that affects the brain’s proper development of social and communication skills, differs greatly in severity and symptoms, and often goes unrecognized, particularly in mildly affected children, and parents don’t generally notice symptoms until the child is 18 months old and clinicians aren’t able to diagnose autism until children start exhibiting the first behavioral and language symptoms of autism at about two years of age.
There is no cure for autism, but experts say that treatment is best delivered as early as possible to prevent or reduce the onset of disabling symptoms associated with the disorder.