the visitor returns walkthrough mutation

When the team analyzed the genes in the mouse brains that were abnormally expressed and compared them to the human genome, two areas pinged. Researchers consider vocalizations a “species-appropriate communication mode,” and this communication problem in mice mirrors the communication problems of the children in the study, he said. “We don’t know for sure what mouse ultrasonic vocalization means to another mouse, but they generate them in social contexts,” Cowan said. Indeed, the mouse model that was given one good copy and one inactive copy of MEF2C showed social deficits, hyperactivity, repetitive behavior and a significant reduction in ultrasonic vocalizations, Cowan said. That the mutations were occurring in this “hub” gene hinted that the mutations were causing problems for the protein to bind to DNA. Those other genes must be activated at just the right time for neurons to mature, form appropriate connections and change in response to experiences, he said. Highly conserved protein regions have barely changed through millions of years of evolution – they remain nearly identical whether in yeast, flies or humans, strongly suggesting they serve a very important function.Īnd this particular protein is a transcription factor, which sits in the nucleus of the cell, binds to DNA and turns on hundreds of other genes, Cowan said. They realized that nearly all the mutations were in the DNA binding region, affecting the most highly conserved portion of the protein MEF2C. Cowan and his team were excited about the opportunity to connect and interested in meeting human patients, Skinner said.Ĭowan said that when they first created a mouse model of MEF2C haploinsufficiency syndrome, they looked to the scientific literature to see what gene mutations had already been found. As he listened, Skinner realized he’d just seen a patient with this gene dysfunction. There to hear the talks was Steve Skinner, M.D., director of the Greenwood Genetic Center. From left, Adam Harrington is a postdoctoral scholar, Chris Cowan is chairman of the Department of Neuroscience, and Catherine Bridges is a M.D./Ph.D. More recently, the paper’s joint lead authors, Adam Harrington, a postdoctoral scholar, and Catherine Bridges, an MUSC medical scientist training program student, both made presentations at a South Carolina Autism and Neurodevelopmental Disorders Consortium conference about their work on MEF2C in mice. When Cowan moved to South Carolina in 2016, he gave a talk at the Greenwood Genetic Center about his latest research findings, including information about MEF2C. He’d also observed a connection to fragile X syndrome, the most common inherited form of autism. He’d previously found the MEF2 family is involved in synaptic pruning, the process by which the brain becomes more efficient as it prunes away redundant or irrelevant synaptic connections this process occurs through young adulthood but is most active in the preschool and elementary school years. However, he noted that most children with this syndrome experience seizures by 20 months old, which could be a trigger for genetic testing and then potential treatment.Ĭowan has been studying MEF2C for more than a decade. It’s not yet clear when interventions could be effective or if there is a developmental point of no return, he said. We can think about ways to introduce more MEF2C into the brain during critical periods of development,” he said.

So, from a therapy standpoint, I think it opens a lot of interesting doors. The individuals have half as much MEF2C as they need. The result in humans includes an inability to use language to communicate, epilepsy, repetitive movements, low muscle tone and breathing problems.Ĭowan said the results of the study raise new prospects for treatment. Basically, one of their two MEF2C genes in each cell is nonfunctioning, and the one non-mutated copy of the gene isn’t powerful enough to regulate brain development the way it should, said Christopher Cowan, Ph.D., chairman of the Department of Neuroscience, whose lab conducted the study. Those patients have a rare form of autism called MEF2C haploinsufficiency syndrome. A collaboration between scientists at the Medical University of South Carolina and clinicians at the Greenwood Genetic Center has yielded new findings about how a particular gene might regulate brain development.Ī paper published in Biological Psychiatry showcases how the researchers connected problems in mice with a defective copy of the MEF2C gene to issues suffered in real life by patients seen at the Greenwood Genetic Center who also have a defective copy of that gene.

The visitor returns walkthrough mutation