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Older fathers 'link' to autism

17:27 Thu Apr 5 2012
AAP

Defective sperm from older fathers may trigger "new" genetic mutations linked to autism, a study has shown.

Researchers found that "de novo", or newly created, mutations played an important role in autistic spectrum disorders (ASDs).

These defects were "overwhelmingly paternal" in origin, said the scientists.

Fathers were four times more likely to generate the mutations than mothers. The gene defects were also "positively correlated" with paternal age.

The findings added to previous research showing that older fathers are slightly more at risk of having an autistic child.

Scientists analysed the DNA of 677 individuals from 209 families with a single child with autism, and 50 unaffected brothers and sisters.

They identified 248 "de novo" mutations, of which 120 were classified as "severe" and likely to produce shortened or malfunctioning proteins.

From this list the researchers focused on 60 mutations most likely to contribute to autism risk.

There was "strong direct evidence" of a "substantially" higher mutation rate in fathers which rose with increasing age.

The US scientists, led by Doctor Evan Eichler, from the University of Washington in Seattle, wrote in the journal Nature: "These observations are consistent with the hypothesis that the modest increased risk for children of older fathers to develop ASD is the result of an increased mutation rate."

The study was one of three autism investigations published in the latest edition of Nature which highlighted the role of "de novo" mutations.

Another paper identified three new genes linked to autism. The third focused on multiple disruptive mutations in autism-linked brain genes.

British expert Doctor Rosa Hoekstra, lecturer in psychology and genetics at the Open University, said: "We already knew that there isn't a 'single gene for autism', but these new research publications suggest that the underlying genetic mechanisms may be even more complex than previously thought.

"These studies show that de novo point mutations - small gene changes that are not inherited from either parent - in the protein coding part of our DNA are common, and that some of these new genetic changes may be implicated in the risk for developing autism.

"A striking result from these studies is the association between new genetic changes and paternal age: de novo mutations seem to be more common in children of older dads; and if a child with autism has such a new genetic mutation, it seems to be much more often of paternal than maternal origin."

Doctor Kevin Mitchell, from the Smurfit Institute of Genetics at Trinity College Dublin, said:

"These studies reinforce the fact that autism is not one disorder - not clinically and not genetically either. Like intellectual disability or epilepsy or many other conditions, it can be caused by mutations in any of a very large number of genes. The ones we know about so far make up maybe 20-25 per cent of cases - these new studies add to that list and also show how far we have to go to complete it."

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