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Most intellectual disability not inherited
A study published online ahead of print in The Lancet finds that most non-syndromic intellectual disability in children is not the result of recessive parental genes, but of newly-arising, non-inherited mutations.
Intellectual disability affects around 1-2% of people and is defined as substantial impairment of cognitive function manifesting in childhood. Non-syndromic means it is not accompanied by recognisable morphological characteristics, and that the genetic basis is usually unknown.
The researchers enrolled 51 children with intellectual disability (most with measured IQ below 60) and their parents along with 20 non-disabled children and their parents as a control group. They compared gene sequences between patients and their parents in order to identify newly-arising variants that had not been inherited.
88% of patients had new variants, compared to 70% of the control group. A much higher proportion of the case group’s variants were associated with loss-of-function (around 40%) compared with 10% in the control group. A third of the patients had new variants located within genes associated with a known intellectual disability syndrome.
After excluding copy-number variants, the authors conclude that some 45-55% of non-syndromic intellectual disability can be accounted for by newly-arising mutations, and that recessive inheritance makes little contribution. They suggest that the significant number of mutations found within genes associated with syndromes amongst the case group could indicate that some do in fact have a known syndrome, but that it had not been identified because their physical characteristics did not match an overly-rigid clinical description.
The implication of this study is that parents of a child with intellectual disability do not in most cases have an increased risk of having further children with similar disabilities, since the condition is more likely to be the result of randomly occurring new mutations rather than parental recessive genes. However, larger-scale and more detailed studies will be needed to produce a risk analysis of any significance for specific cases.