Scientists have discovered that two genes individually implicated in rare forms of autism are also jointly linked to more general forms of autism.
The genes encode the proteins NHE6 and NHE9, which are responsible for biochemical exchanges in the endosomes of cells.
Brown University researchers and their colleagues found a specific pattern of misregulation of those two genes - NHE9 is up-regulated and NHE6 is down-regulated - in the brains of children with autism compared to the brains of non-autistic children.
"These genes play a role, not just in the rare forms of autism but also in the generalised pathology of autism," said Dr Eric Morrow, professor of biology and professor of psychiatry and human behaviour at Brown University, the paper's senior author.
"In autism I think people get overwhelmed because there are hundreds of different genes. One of the important things is to find points of convergence where there are events that might be common across different forms," Morrow said.
The new study suggested that misregulation of NHE6 and NHE9 is one such event.
The research is based on a statistical analysis of messenger RNA samples from a bank of brain tissue donated posthumously by some children who had autism and some who did not.
Messenger RNA is a key molecular player in the process of gene expression, making it an indicator of how gene expression was regulated in the cerebral cortex of each of the children.
Lead author Matthew Schwede pored over the raw data, which was made available from a 2011 study led by co-author Daniel Geschwind and Irinia Voineagu of the University of California-Los Angeles.
Schwede's findings about the NHE genes caught Morrow's attention in particular, because Morrow has been studying the NHE6 and NHE9 genes and the rare autism forms they cause.
"When we realised that some genes of interest for our lab were altered in the cerebral cortex, we focused the analysis on these genes in particular and how they were related to other processes," Schwede said.
Schwede made a second key finding: a strong and significant correlation between the misregulation of the NHE genes and the down-regulation of synapse genes, which is known to occur in autism.
Schwede's purely statistical analysis does not explain the physiology of how up-regulation of NHE9 and down-regulation NHE6 would affect synapse formation or general autism, but Morrow's biology group has a clear next step: to observe the neural and behavioural effects in the lab of misregulation of those genes in various experimental systems.
The study was published in the journal Molecular Psychiatry.
