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Migraine mutations reveal clues to biological basis of disorder
Date:6/30/2008

Fifteen percent to 20 percent of people worldwide suffer from migraines excruciating headaches often presaged by dramatic sensations, or "auras." By studying a rare, inherited form of migraine, researchers at Vanderbilt University Medical Center have found clues to the biological basis of the painful, debilitating disorder.

In the Proceedings of the National Academy of Sciences, Alfred George Jr., M.D., and colleagues report that genetic mutations linked to this rare form of familial migraine alter the function of sodium channels protein "tunnels" through brain cell membranes involved in the electrical conduction of nerve impulses.

The findings identify cellular events that may prompt migraines specifically the aura that precedes them and suggest that medications targeting sodium channels might warrant a closer look as potential treatments for some forms of migraine.

George and colleagues investigated the physiological basis of a severe, inherited form of migraine called "familial hemiplegic migraine type-3" (FHM3). The aura associated with FHM3 often includes a transient weakness or paralysis of one side of the body.

FHM3 is caused by mutations in a sodium channel gene, SCN1A. Researchers in Europe had identified three mutations associated with the condition and contacted George about studying the cellular effects of these mutations.

"We were already studying this gene, SCN1A, in genetic forms of epilepsy," said George, the Grant W. Liddle Professor of Medicine, professor of Pharmacology, and the director of the Institute of Integrative Genomics. "This was a great opportunity to investigate the physiology of SCN1A mutants linked to another episodic neurological disorder."

George and colleagues genetically inserted the mutant sodium channels into cultured human cells and recorded the cells' electrical properties the key function modulated by sodium channels.

One mutant, called L1649Q, f
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Contact: Craig Boerner
craig.boerner@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert

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