Recent research has shed new light on a particular gene mutation linked to a rare form of autism.
A new study is helping scientists better understand the link between the mutation of a gene called MEF2C and a rare form of autism called MEF2C haploinsufficiency syndrome.
The study, which appears in the journal Biological Psychiatry, is the result of a collaboration between the Medical University of South Carolina (MUSC) in Charleston and the Greenwood Genetic Center, also in South Carolina.
In general, people have a pair of MEF2C genes. However, for people with MEF2C haploinsufficiency syndrome, only one of them functions properly. The other is not powerful enough to mediate brain development as it should normally.
According to an article in the journal Neurogenetics, MEF2C haploinsufficiency syndrome is “associated with intellectual disability, autistic features, epilepsy, and abnormal movements.”
Although scientists know that a deficiency in the MEF2C genes is responsible for MEF2C haploinsufficiency syndrome, they do not yet know exactly how the genes regulate brain development.
To explore this issue, the researchers conducted an animal study. In it, they altered the genes in mice and compared the effects with typical symptoms in humans.
After reviewing the literature, they found that the mutations in the Mef2c gene affected its DNA binding region. This could affect hundreds of other genes that require this binding to be expressed.
When the scientists compared the abnormal expression of genes in the mice with human genes, they noticed changes in two key areas: neuronal cells and microglia cells. When they modified genes in these cells specifically, they saw different symptoms in the mice.
In general, when the researchers modified the mice’s Mef2c genes, they presented with similar symptoms as humans who had MEF2C haploinsufficiency syndrome, including a reduction in ultrasonic vocalizations, which are those that are too quiet for humans to hear.
According to senior study author Dr. Christopher Cowan, chair of the Department of Neuroscience at MUSC, “We don’t know for sure what mouse ultrasonic vocalization means to another mouse, but they generate them in social contexts.”
Dr. Cowan notes that the value of the recent research is in the way it draws attention to the need to understand the interconnecting effects of brain cells.
“For the field,” he says, “I think it’s important because it’s starting to help us appreciate that neurodevelopmental [conditions] are probably a convergence of dysfunction or altered development of multiple different cell types.”
“This has treatment implications as well, because you can’t just target the neuronal population. You can’t just target microglia. You’re probably going to have to think about the cluster of different cooperating cell types in the brain that lead to a typically functioning brain,” he adds.
The collaboration between MUSC and the Greenwood Genetic Center occurred after Dr. Steve Skinner, director of the latter, heard a talk by lead study authors Adam Harrington, a postdoctoral scholar, and Catherine Bridges, a student in the MUSC medical scientist training program.
Dr. Skinner had recently seen a patient with a dysfunctional MEF2C gene, and the scientists recognized that working with humans who may have MEF2C haploinsufficiency syndrome could be valuable in furthering the science to understand how the syndrome works.
“We know the problem. The individuals have half as much MEF2C as they need. So, from a therapy standpoint, I think it opens a lot of interesting doors. We can think about ways to introduce more MEF2C into the brain during critical periods of development.”
– Dr. Christopher Cowan
The research has also benefited from the input of families across the world. The internet allows families to connect with other families who have children with the syndrome, which has helped make evident some aspects of it that were previously unclear.