Intellectual disability affects 1 to 3 percent of children worldwide, half of whom are born to parents of normal intelligence. Researchers have discovered that most of these cases of "sporadic intellectual disability" result from new, random mutations arising spontaneously in the children's genes, not from faulty recessive genes inherited from their parents.
The researchers say their finding is one of the first steps in understanding the underlying causes of this condition (also known as mental retardation), which is marked by having an IQ below 70, and is — perhaps surprisingly — the costliest of all health problems. Understanding the cause may eventually lead to new therapies, they said.
Everyone is born with several de novo mutations, or accidental changes in DNA (such as the deletion or duplication of a base pair) not found in one's parents' DNA. Most of the time, these mutations occur in non-crucial parts of DNA and thus cause minimal harm, but sometimes the mutations can have drastic consequences, such as by impairing the function of a gene that influences cognitive development. The new study finds that this random bad luck accounts for the majority of cases of sporadic intellectual disability.
For the study, lead author Anita Rauch of the University of Zurich in Switzerland and colleagues sequenced the exomes (subsets of the DNA) of 51 severely intellectually disabled children, who had IQs below 50, and compared these with the exomes of their able-minded parents. As a control, the scientists also sequenced and compared the exomes of 20 able-minded children and their parents. [The Smarter Sex? Women's Average IQ Overtakes Men's]
Compared with the children in the control group, the disabled children turned out to have slightly more de novo mutations. This may be because they had older fathers, on average — a recent study in the journal Nature showed that a father's age strongly affects de novo mutation counts — but more important was which parts of their DNA happened to have mutated.
"People with intellectual disability had slightly more de novo mutations than controls, but more significantly [they] had more mutations with drastic consequences, which likely happened to them by chance," Rauch told LiveScience. De novo mutations appearing in 11 genes known to be associated with intellectual disability and six candidate genes believed to play a role altogether appeared in 55 percent of the cases studied.
Because other genes that were affected by new mutations have roles that are not well-known, the researchers conjectured the percentage of the cases of sporadic intellectual ability caused by de novo mutations was probably even higher than 55 percent. According to study co-author André Reis of Karls Universität in Tübingen, Germany, the results suggest that only a small proportion of cases are caused by autosomal recessive gene inheritance, where affected children inherit one copy of the faulty gene mutation from each parent. Before the study, this was believed to be the primary cause.
The findings appear in a paper published online Sept. 26 in the medical journal The Lancet. "Future studies have to address the exact [mechanisms] underlying the various gene defects which may than lead to new possibilities of treatment," Rauch said.
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Natalie Wolchover was a staff writer for Live Science from 2010 to 2012 and is currently a senior physics writer and editor for Quanta Magazine. She holds a bachelor's degree in physics from Tufts University and has studied physics at the University of California, Berkeley. Along with the staff of Quanta, Wolchover won the 2022 Pulitzer Prize for explanatory writing for her work on the building of the James Webb Space Telescope. Her work has also appeared in the The Best American Science and Nature Writing and The Best Writing on Mathematics, Nature, The New Yorker and Popular Science. She was the 2016 winner of the Evert Clark/Seth Payne Award, an annual prize for young science journalists, as well as the winner of the 2017 Science Communication Award for the American Institute of Physics.