Gavin Rumbaugh Ph.D., NARSAD Young Investigator Grantee and assistant professor at the Scripps Research Institute, led new research finding that mutations in a single gene, known to cause intellectual disability and increase the risk of developing autism spectrum disorders, severely disrupt the organization of developing brain circuits during early childhood. The study helps explain how genetic mutations can cause profound cognitive and behavioral problems and points toward possible early intervention techniques to repair the mutations and prevent the damage from occurring.
Dr. Rumbaugh said, "In this study, we did something no one else had done before. Using an animal model, we looked at a mutation known to cause intellectual disability and showed for the first time a causative link between abnormal synapse maturation during brain development and life-long cognitive disruptions commonly seen in adults with a neurodevelopmental disorder."
The study was published in the Nov. 9, 2012, issue of the journal Cell and reported that mutations in the gene that encodes the synaptic protein SynGAP1 (short for synaptic Ras GTPase activating protein 1) are responsible for disabilities in approximately one million people worldwide. "There are a few genes that can't be altered without affecting normal cognitive abilities," Rumbaugh said. "SynGAP1 is one of the most important genes in cognition -- so far, every time a mutation that disrupts the function of SynGAP1 has been found, that individual's brain simply could not develop correctly. It regulates the development of synaptic function like no other gene I've seen."
Interestingly, inducing these mutations after the critical development period was complete had virtually no impact on normal synapse function and repairing these pathogenic mutations in adulthood did not improve behavior or cognition. These results imply that very early intervention is essential in neurodevelopmental disorders, particularly for cognitive problems. The team is now aggressively searching for the optimal period during development in which repairing these mutations is most beneficial.
Read more about Dr. Rumbaugh's research