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ORNL finds common genetic cause for epilepsy, migraine
OAK RIDGE, Tenn.,
Jan. 20, 1997
Migraine and epilepsy have more in common than researchers thought, says Lisa Stubbs, a genetics researcher at the Department of Energy's (DOE) Oak Ridge National Laboratory (ORNL).
Stubbs and colleagues at ORNL recently completed a study in which they isolated, mapped and studied effects of the chromosome 8 Cacnl1a4 gene found in mutant "tottering" mice, which have been studied extensively as models for human epilepsy. The specific region of the mouse gene has a counterpart in humans (a chromosome 19 region) that had previously been identified as causing episodic ataxia (spells of incoordination) and migraines in people.
ORNL's findings suggest a common genetic cause for migraine, ataxia and epilepsy, meaning that tottering mice - aptly named for their lack of muscle control - represent mouse models for both diseases. These models, developed with the help of a human chromosome 19 map from the Human Genome Center at Lawrence Livermore National Laboratory (LLNL), are likely to be useful for further studies.
"Knowing what it is that causes epilepsy and migraines could help us get a cure or prevent future cases," Stubbs said. "It could also prove very valuable for testing drugs."
Now that researchers have identified the likely cause for migraine and epilepsy, the focus turns to how the mutation affects cells' function.
"The implicated gene affects the movement of calcium into and out of specific brain cells," Stubbs said. "This calcium movement regulates the release of neurotransmitters, which are critical elements in the communication network among nervous system cells.
"Calcium flow also plays a critical role in the growth and internal regulation of nerve cells."
Further research into the structure and function of the gene will improve diagnosis and may aid in development of new treatments for migraine.
In addition to the role of genes suggested by family-, twin- and population-based studies, such other factors as emotional stress and certain foods and additives have been associated with migraine attacks.
Isolation of the human episodic ataxia/migraine gene was reported in an independent study done by LLNL and Leiden University in The Netherlands. In that study, researchers cloned the human gene CACNL1A4, which contained the mutations associated with ataxia spells and a specific type of migraine (familial hemiplegic migraine). Researchers noted that although that type of migraine is rare, variations in the same gene may predispose people to the more common migraine, which affects an estimated 24 percent of women and 12 percent of men.
Funding for this research was provided by DOE's Office of Health and Environmental Research.
ORNL, one of DOE's multiprogram research facilities, is managed by Lockheed Martin Energy Research Corp.