A new study has identified 27 different genetic regions where rare copy number variations—missing or extra copies of DNA segments—were found in the genes of children with autism spectrum disorders, but not in the healthy controls. The findings, published in the open-access journal PLoS Genetics, add new pieces to the complex autism inheritance puzzle.

 

Autism spectrum disorders or ASDs are common neurodevelopmental syndromes with a strong genetic component. ASDs are characterized by disturbances in social behavior, impaired verbal and nonverbal communication, repetitive behaviors and/or a restricted range of interests. The genetics underlying ASDs is complex and remains poorly understood.

 

Researchers at the University of Pennsylvania School of Medicine and the Children's Hospital of Philadelphia compared genetic samples of 3,832 individuals from 912 families with multiple autistic children against genetic samples of 1,070 disease-free children. Besides the identification of 27 regions harboring rare variants in children with ASDs, the study also found two novel genes where variations were thought to be important in synaptic function and neurological development. Key variants on these genes were passed down in some, but not all, of the affected individuals in families.

 

“We focused on changes in the exons of DNA—protein-coding areas in which deletions or duplications are more likely to directly disrupt biological functions,” says study leader Hakon Hakonarson. “We identified additional autism susceptibility genes, many of which belong to the neuronal cell adhesion molecule family involved in the development of brain circuitry in early childhood.” He adds that the team discovered many “private” gene mutations, those found only in one or a few individuals or families—an indication of genetic complexity, in which many different gene changes may contribute to an autism spectrum disorder.

 

Hakonarson and co-author Maja Bucan say the latest findings reinforce the view that multiple gene variants, both common and rare, may be interacting to cause the heterogeneous group of disorders included under autism spectrum disorders. “We are finding that both inherited and new, or de novo, genetic mutations are scattered throughout the genome,” says Bucan, “and it is becoming clear that different combinations of these variations contribute to autism susceptibility.”