Do older dads pass on autism risk?

A new study shows that mutations that can cause autism are more often from the affected child’s father (at a four-to-one ratio), and correlate with his age. The University of Washington researchers’ results are reported in the journal Nature. These findings, they say, support other studies that show older fathers have a slightly increased risk of having a child with an autism spectrum disorder. The researchers have been studying autism in children who have no family history of this or related impairments—so called “sporadic autism”—and also why autism varies in its symptoms and severity. By focusing on “sporadic autism”, the researchers sought to evaluate a specific genetic model for autism risk, namely the appearance of new mutations in children with autism that were not found in either parent. “It is important to point out that in each generation there is on average one new coding mutation per child and not all of these will cause developmental problems,” says Brian J. O’Roak, a senior fellow in the Department of Genome Sciences working with senior authors Jay Shendure and Evan Eichler. “However, in the case of children with autism, what we are finding is disruptions in many genes that are known to directly interact and also look similar to genes previous associated with autism.” What is also very clear from this study and two additional studies appearing concurrently in the same issue of Nature is that autism risk mutations are scattered across many genes. In the University of Washington study, recurrent protein-altering mutations were discovered in only two genes. The data suggest that, at the molecular level, there are many different forms of autism and that the term “autism spectrum disorder” is better thought of as an umbrella disorder with many root causes. The authors predict that although no single gene will account for more than 1 percent of autism, collectively all of these rare mutations will account for much of the genetic basis of the disease. Among the other genes they discovered with new mutations in children with autism, several have been previously implicated in intellectual disability and developmental delay. This indicates, the authors say, that the divisions clinicians made between these various types of diseases in children may not readily translate into differences at the molecular level. The researchers add that it is still uncertain whether there are subsets of people with autism who share a common or strongly related causative mechanism in their underlying molecular biology, or how large those groups might be.