Severe retardation isn't caused by genes handed down from parents — it's caused by new genetic mutations that first appear in the child, according to a new study.
Severe intellectual disability, also known as nonsyndromic mental retardation, is the most common form of mental retardation. Children or adults with the condition have no physical abnormalities, but have IQs of less than 50. It affects up to 2 percent of children worldwide.
The new findings, which appear in the Oct. 3 online issue of the New England Journal of Medicine, dovetail with a similar study published last week in The Lancet.
In the latest study, researchers Joep de Ligt and colleagues at Radboud University, in the Netherlands, used a sophisticated type of gene screen called exome sequencing on 100 people with severe intellectual disabilities and their unaffected parents.
The investigators found that there were gene mutations in the patients' DNA samples, but they were new ones that were not passed down from their parents. All in all, they identified 79 genetic mutations in 53 patients, many of which had never been seen before. They confirmed their findings in another group of 765 people with intellectual disability.
Joseph Devaney, principal investigator at the Center for Genetic Medicine Research at the Children's National Medical Center in Washington, D.C., said that the new technology allows researchers to dig deeper into genes.
"This removes the idea of looking at a candidate gene or region and opens it up to look at everything," he said. "We are going from a 10,000-foot view to street-level view and we are seeing gene changes that we have never seen before."
The new findings may help pave the way for screening tests or new therapies that target these genes, said Devaney, who was not involved with the study. "These screens would be something that we could potentially do in early pregnancy, but we are a long way from that," he added.
In an accompanying journal editorial, Dr. Heather Mefford, a pediatrician in the division of genetic medicine at the University of Washington in Seattle, pointed out that "these are exciting times in medical genetics, and exome sequencing is revolutionizing the field." The new study, she wrote, "shows how the technology can be used successfully in a diagnostic setting for patients with severe intellectual disability."
These new gene screens do identify a host of mutations, and the challenge is trying to determine which ones play a causative role and which ones don't, he added. "We need to sort out the smoking guns from the red herrings," Adesman said.
"It's not because of a single drink of alcohol you took during pregnancy or a stumble down the stairs — these are new genetic mutations that appear for the first time in the affected child," he said.
The new research should be reassuring to parents who had feared that genes they carried were responsible for their child's retardation, said Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at Steven and Alexandra Cohen Children's Medical Center of New York in New Hyde Park.