NARSAD Grantee Eric M. Morrow, M.D., Ph.D. of Brown University and his collaborators have identified a new genetic pathway linked to autism. The research team studied rare forms of autism and found that two genes individually associated with these rare forms are also jointly linked to more general forms of autism. Findings of the study were published March 19, 2013 in Molecular Psychiatry.
The two genes studied encode the proteins NHE6 and NHE9, which are responsible for biochemical exchanges in the endosomes (a network of cellular vesicles). Mutations in the NHE6 gene are known to cause the rare Christianson Syndrome, while mutations in the NHE9 gene lead to a rare and severe form of autism with epilepsy.
The researchers conducted a statistical analysis of messenger RNA samples from a 2011 study by their fellow authors and NARSAD Grantees Daniel H. Geschwind, M.D., Ph.D., and Irinia Voineagu, M.D., Ph.D., of the University of California–Los Angeles. From a bank of brain tissue donated posthumously by some children who had autism and some who did not, the researchers focused in on these two genes to identify how they were expressed in the children’s brains. They found that NHE9 was up-regulated while NHE6 was down-regulated in children who were diagnosed with general forms of autism compared to those who were not. They also found a strong correlation between the misregulation of the NHE genes with the down-regulation of synapse genes, known to occur in general forms of autism.
"These genes play a role, not just in the rare forms of autism but also in the generalized pathology of autism," said Dr. Eric Morrow, professor of biology and professor of psychiatry and human behavior 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." NARSAD Grantee Karoly Mirnics, M.D., of Vanderbilt University was also a study author.
Read the study announcement
Read the study abstract in Molecular Psychiatry