Pathogenic roles of paternal-age-associated mutations in autism

Advanced paternal age has been linked to a higher incidence of autism in children, but the reasons for this association are not known. A substantial fraction of inherited autism risk is thought to arise de novo, through new gene variants that form through mutations in the reproductive cells of the father.

This process could provide a partial explanation for why children who are affected by the disorder often have parents who are not. Such gene variants can appear at any stage of maturation of the reproductive cells (i.e., from the most primitive stem cells to mature sperm).

Marco Seandel of Weill Cornell Medical College in New York and his colleagues are planning to investigate the earliest of these genetic alterations that elevate the risk of autism.

Seandel and his team aim to test the hypothesis that recently discovered autism-linked gene variants enhance the competitiveness of testicular stem cells in such a way as to increase the likelihood that these particular variants will be transmitted to the child. Using testicular stem cells derived from adults, Seandel’s group plans to study the functional effects of specific gene variants associated with autism.

The researchers hope that this work will yield insight into the earliest genetic events in autism and provide a rapid means to identify novel signaling pathways that contribute to the neurodevelopmental abnormalities seen in autism.