A new research study discovers several sporadic genetic mutations in children with autistic spectrum disorder.
University of Washington researchers used new molecular biology techniques to discover the mutations. The research is published online in the journal Nature Genetics.
Dr, Brian O’Roak and colleagues analyzed the genetic makeup of 20 individuals with autism spectrum disorder and their parents.
Autism spectrum disorders encompass a range of social impairments in language, communicating and interacting with others, repetitive behaviors, and engrossing fascinations. The condition can be mildly to severely disabling.
The researchers found 21 newly occurring mutations, 11 of which altered proteins. Proteins altered by genetic mutations may hold clues to the biological pathways involved in the development of the disease. The abnormal proteins or the pathways they affect could draw interest as targets in the design of preventive or treatment drugs.
In four of the 20 families studied, O’Roak and colleagues identified disruptive new mutations that are potentially causative for autism. In examining the clinical data on the child in each of the four families, they learned that these children were among the most severely affected of the study group, both in intellectual disability and in their autistic features.
The findings suggest that these new sporadic disruptive genetic mutations could play a significant factor in the underlying mechanisms and severity of autism in perhaps 20 percent of the cases in which no larger family history of autism exists.
In some cases, the combination of newly appearing mutations and those inherited from the parents may worsen the severity of the disorder.
In this study, many of the discovered mutations were located in genome areas that were highly conserved during evolution. These parts of the genome likely play a fundamental role in the biology of many animals, including humans. Mutations in these regions tend to have significant repercussions.
“Consistent with the complexity of autism and its symptoms, the new mutations were identified in several different genes,” lead author O’Roak said.
Moreover, many of these mutated genes have already been associated with other brain disorders, including epilepsy, schizophrenia and intellectual disability — reflecting a surprising genetic overlap.
Still, the researchers say that are not sure what the genetic overlap means. It could point to common underlying mechanisms in the development of these neurological diseases, or different manifestations stemming from similar genetic lesions.
Another view is that the mutations may stem from other factors, such as environmental triggers or other genes in a person’s make-up that influence how and when genes operate, whether or not a disease will appear in a genetically susceptible individual, and what type of disease it will be.
How and why sporadic mutations such as these originate is as yet unknown. However researchers are uncovering clues about risk factors.
In six of the affected children in this study, the scientists were able to trace the original genes that were later mutated in the child back to the father’s half the child’s genome, and in one case to the mother’s half. This findings support population studies showing that autism is more common among children of older parents, especially older fathers.
Researchers say the identification of mutations is a positive step toward understanding autism and the interaction of genetic and environmental factors.
Source: University of Washington