Researchers discovered de novo mutations in the TBR1 gene of children with severe autism - a gene linked to brain development.
Image credit: Radboud University Nijmegen
Rates of autism have increased significantly in recent years, with 1 in 68 children in the US diagnosed with the disorder, compared with 1 in 150 back in 2000.
Increasingly, research suggests severe cases of autism may stem from gene mutations that develop in the egg or sperm, rather than mutations that are inherited from parents. These are known as de novo mutations.
In this latest study, researchers from the Nijmegen Max Planck Institute for Psycholinguistics in the Netherlands and the University of Washington found that children with severe autism had de novo mutations in a gene called TBR1, which they say is important for early brain development.
Furthermore, they linked this gene to another called FOXP2, which they say is related to language development.
A 'striking confirmation' of how strongly de novo mutations affect brain development
To reach their findings, the team used a number of next-generation DNA sequencing techniques to analyze the genomes of thousands of unrelated children with severe autism.
They found that, compared with inherited mutations in the TBR1 gene, de novo mutations appeared to have much more of a destructive impact on TBR1 function. "De novo truncating and missense mutations disrupt multiple aspects of TBR1 function, including subcellular localization, interactions with co-regulators and transcriptional repression," the researchers explain.
Commenting on this discovery, co-author Dr. Pelagia Deriziotis, of the Nijmegen Max Planck Institute for Psycholinguistics, says:
"This is a really striking confirmation of the strong impact that de novo mutations can have on early brain development."
Link between TBR1 and FOXP2 'very interesting'
The team notes that to function properly, the human brain requires a number of genes and proteins to work together. Therefore, they set out to identify the genes that interact with TBR1.
They found a direct link between TBR1 and FOXP2 - a gene believed to play an important role in speech and language disorders. Furthermore, the team found that mutations in either one of these genes breaks the link.
"Think of it as a social network for proteins," says Dr. Deriziotis. "There were initial clues that TBR1 might be 'friends' with FOXP2. This was intriguing because FOXP2 is one of the few proteins to have been clearly implicated in speech and language disorders. The common molecular pathway we found is very interesting."
Senior author Simon Fisher, director at the Nijmegen Max Planck Institute for Psycholinguistics, says it is "very exciting" to discover such links. "By coupling data from genome screening with functional analysis in the lab, we are starting to build up a picture of the neurogenetic pathways that contribute to fundamental human traits," he adds.
Commenting on their overall results, the researchers say:
"These findings support the hypothesis that de novo mutations in sporadic autism have severe functional consequences. Moreover, they uncover neurogenetic mechanisms that bridge different neurodevelopmental disorders involving language deficits."
Medical News Today recently reported on a study from Columbia University Medical Center in New York, NY, revealing children with autism have too many synapses in their brain, which can affect brain function.