New research published Online First in The Lancet suggests that a high proportion of severe intellectual disability results from genetic causes that are not inherited. These findings are good news for parents, indicating a low risk of passing on the disorder to further children.
Intellectual disability affects between 1% and 2% of children worldwide. Although a handful of genes that appear to cause some cases of intellectual disability have been identified, the genetic causes of the disorder in most people remains unclear, especially those with non-syndromic types which have no obvious physical signs and cause up to 50% of intellectual disability worldwide.
Some evidence suggests that de novo (new) mutations, that show up for the first time in affected children but are not found in their parents, might be a common cause of the disorder.
As a joint effort by the German Mental Retardation Network led by André Reis from the Institute of Human Genetics, University of Erlangen-Nuremberg, Germany, the current study used a new technique known as exome sequencing to look for mutations that are not inherited but newly formed in 51 children with unexplained severe non-syndromic intellectual disability (an IQ <50) and their unaffected parents from nine centres across Germany and one center from Switzerland.
The researchers found that children with intellectual disability carried a significantly higher number of likely disease-causing mutations in their genome than those without the disorder. New mutations in both 11 known and six new candidate genes were estimated to cause intellectual disability in up to 55% of the cases studied.
"Although believed to be relatively common in intellectual disability, these results suggest that only a small proportion of cases of sporadic intellectual disability are likely to be inherited in autosomal recessive fashion (affected children inherit one copy of the faulty gene mutation from each parent)", explains Reis.
Writing in a linked Comment, Jozef Gecz and Eric Haan from the University of Adelaide in Australia point out, "Copy number variant profiling and whole-exome sequencing should resolve most (>60%) cases of severe intellectual disability. The remaining cases might be more complex, with contributions from multiple genes, environmental factors, or mutations in non-coding regions of the genome. Whole-genome sequencing technology has the potential to become the first-line diagnostic test for many disorders, and particularly intellectual disability."
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