Genetic Mutation Damages Young Brains, Causes Epilepsy

According to a recent study published in Neuron, a specific mutation in one key gene interferes with early brain development and even causes epilepsy.

Using mouse models, Gavin Rumbaugh and his co-contributors at The Scripps Research Institute and the University of California isolated mutations of a gene called Syngap1. The researchers explained that performing such modifications in young mice prevented significant brain damage later in life.

“We conclude that reduced cognition in Syngap1 mutants is caused by isolated damage to developing forebrain glutamatergic neurons,” the authors wrote. “This damage triggers secondary disruptions to synaptic homeostasis in mature cortical pyramidal cells, which perpetuates brain dysfunction into adulthood.”

In previous studies, Sygnap1 was identified as a leading cause of intellectual disabilities, which affect 1-3% of the global population. Furthermore, studies have shown Syngap1 mutations are indiscriminate, as they are sporadic and non-hereditary in nature. Specifically, mouse models demonstrated Syngap1 mutations damage glutamatergic neurons that are formed in young brains.

According to the authors of the present study, repairing Syngap1 mutations during the development of glutamatergic neurons prevented cognitive damages in adulthood, though “repairing the gene in other kinds of neurons and in other locations had no effect.”

“Here, we found that haploinsufficiency restricted to forebrain glutamatergic neurons was sufficient to disrupt cognition and removing mutations from this population prevented cognitive abnormalities,” the researchers noted. “In contrast, manipulating Syngap1 function in GABAergic neurons had no effect on cognition, excitability, or neurotransmission, highlighting the specificity of Syngap1 mutations within forebrain excitatory neurons.”

Due to advances in modern medicine, it is now possible to scan a child’s genetic code and mutations even before birth, which Rumbaugh said opens the door for effective preventive and early care.

“Our research suggests that if Syngap1 function can be fixed very early in development, this should protect the brain from damage and permanently improve cognitive function,” co-contributor Emin Ozkan said.