Study finds mutations that may cause autism

CHICAGO— A sweeping study of hundreds of families with autism has found that spontaneous mutations can occur in a parent’s sperm or egg cells that increase a child’s risk for autism, and fathers are four times more likely than mothers to pass these mutations on to their children, researchers said Wednesday. The results of three new studies, published in the journal Nature, suggest mutations in parts of genes that code for proteins, called the exome, play a significant role in autism. While these genetic mistakes can occur across the genetic code, and many are harmless, they can cause big problems when they occur in parts of the genome needed for brain development. One of the three teams found these glitches may result in a five- to 20-times higher risk 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. The teams also identified several hundred new suspect genes that could eventually lead to new targets for autism treatments. Autism encompasses a wide spectrum of disorders, ranging from profound inability to communicate and mental retardation to relatively mild symptoms, as in Asperger’s syndrome. In the United States, an estimated 1 in 88 children have autism, according to the latest figures from the U.S. Centers for Disease Control and Prevention, and Canadian experts say the numbers are likely similar here.

Scientists previously have found dozens of genes that may raise the risk of autism. But genetic causes only explain about 10 per cent of cases, and recent studies have pointed to environmental factors, possibly arising at conception, as a potential trigger.

Joseph Buxbaum, director of the Seaver Autism Center at Mount Sinai School of Medicine in New York and a co-author of one of the studies, said the combined results from the three studies suggest some 600 to 1,200 genes may contribute the risk of developing autism. The trick will be identifying specific networks in the brain in which these genes interact, so that researchers can begin to develop new treatments.

One of the studies by Dr. Evan Eichler and colleagues at the University of Washington in Seattle found that new mutations occurred four times more frequently in sperm cells than in egg cells, and the older the father, the more likely he was to have sperm with these spontaneous mutations.

One possible reason for this, Buxbaum said, is that men make sperm every day, and this high turnover rate increases the chance for errors to occur in the genetic code that could be passed on to their offspring.

“It tells us that sperm production is an imperfect process,” Buxbaum said. “As you get older, there are more and more chances for problems.”