Families

The GAD2(glutamate decarboxylase 2) gene provides instructions for making a protein called GAD65, which helps the brain produce γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in our brain. GAD65 is mainly active at nerve endings, where it helps produce GABA during periods of increased synaptic demand during stress for example. We describe four children from three unrelated families in which both copies of the GAD2gene do not work properly. These children have a newly recognized condition characterized by early-onset epilepsy, with seizures that are most severe in the first months of life, along with developmental delay, mild to moderate learning difficulties, and autism spectrum disorder.

To better understand this condition, researchers created a mouse model lacking GAD65. These mice showed the same types of symptoms seen in children, including seizures and other brain-related changes. The strong similarity between the human and mouse findings shows that GAD2is very important for normal brain development and for preventing seizures.