More than 60 percent of people who suffer from Timothy syndrome also suffer from autism spectrum disorder (ASD). Researchers from California and Japan began to generate stem cells from those with Timothy syndrome in order to gain further insight into the neurological causes of autism when the cells are differentiated into neurons.
The study published in Nature Medicine, explained that Timothy syndrome is caused by a genetic mutation that changes one amino acid in a calcium channel expressed in the brain. Therefore the neurons secrete twice as much dopamine and three times as much norepinephrine than control neurons. Being that these neurotransmitters have important social functions, their increased synthesis could play a role in the development of autism.
The Timothy cells also had an altered profile of neuronal differentiation markers, with the changes suggesting that Timothy neurons would preferentially target different areas of the brain. This is consistent with an emerging idea among those who study ASDs that they arise from defects in the connectivity between cortical areas.
The autism seen in Timothy syndrome is unusual, because it is caused by a single, known genetic mutation. Now that some of the functional steps between the genetic mutation and the neurodevelopmental disorder have been elucidated in this study, perhaps they can isolate the causes of autism from those of Timothy syndrome.