A new study published in Nature Communications on a rare genetic disease provides insights into autism, epilepsy and cognitive impairment.
The disorder, tuberous sclerosis, causes benign tumors on the skin and multiple organs, including the heart, kidneys and lungs. About half of people with tuberous sclerosis also have autism spectrum disorder and roughly 90% have seizures.
“Tuberous sclerosis is caused by mutations in two genes that turn off a protein called ‘MTOR,’” Dr. Daniel Vogt said. “When MTOR is on at the wrong times, autism is a consequence. Understanding how MTOR regulates development and function of brain cells is important in understanding both how autism develops and the neuropsychiatric symptoms of tuberous sclerosis.”
As part of the study, Vogt and his team created knockout mice that lacked TSC1, one of the two genes responsible for tuberous sclerosis. The scientists found that certain cells had higher levels of MTOR. The team validated these findings by comparing them to other mice that still had the TSC1 gene.
“This analysis made clear MTOR is really important in the pathway,” Vogt said. “This was really a big surprise for the field.”
The team also found that in mice without the TSC1 gene had an imbalance in normal brain activity that causes seizures. The authors believe this may contribute to the relatively high likelihood of epilepsy in individuals with tuberous sclerosis.