New clue found for fragile X syndrome-epilepsy link

fragile X syndrome

People with fragile X syndrome, the most common inherited form of intellectual disability, often develop epilepsy, but so far the underlying causes are unknown.

Emory researchers have now discovered a potential mechanism that may contribute to the link between epilepsy and fragile X syndrome.

The protein that is missing in fragile X syndrome, FMRP, controls the production of a protein that regulates electrical signals in brain cells, the research team has found. In mice missing FMRP, brain cells produced less of a protein called Kv4.2, which regulates the excitability of neurons in the hippocampus, a region of the brain important for learning and memory. A mutation of the gene encoding Kv4.2 leads to temporal lobe epilepsy in people.

FMRP is known to regulate several genes, and for many of those genes, FMRP normally acts as a brake by interfering with the step in which RNA is made into protein. In FMRP’s absence, runaway protein production occurs at the synapses, junctions between brain cells where chemical communication occurs. Kv4.2 appears to be an exception, because in FMRP’s absence, less Kv4.2 protein is produced.

In laboratory tests, drugs that tamp down glutamate signaling could partially restore levels of the Kv4.2 protein in mice missing the fragile X protein, says Emory cell biologist Gary Bassell, who headed up the research team.

Not all individuals with fragile X syndrome develop epilepsy. The loss of FMRP doesn’t shut Kv4.2 production off completely, and other genetic variations and environmental factors probably contribute to the development of epilepsy in people with fragile X syndrome, Bassell says.

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Emory Medicine Fall 2011