(HealthScoutNews) -- Researchers have identified a gene that causes a rare form of epilepsy in which patients experience sound hallucinations before their seizures.

A report in the February issue of Nature Genetics reveals that mutations in the leucine-rich, glioma-inactivated 1 gene (LGI1) cause a rare form of the disorder known as autosomal-dominant partial epilepsy with auditory features (ADPEAF).

An expert in the genetics of epilepsy praised the discovery. "Finding a gene is exciting, because it gives us information about which signaling pathway in the brain is at the cause of this particular form of epilepsy," says Dr. Jeffrey Noebels, a neurologist and molecular geneticist at Baylor College of Medicine in Houston. "Finally, it's a starting point to try to understand what causes the disease and, also, which molecules might be useful therapeutically to prevent it."

Epilepsy is a neurological disorder in which the electrical impulses that control the brain occasionally malfunction, causing various types of seizures. There is no known cure, although treatment exists in the form of medications, surgery or a special diet. More than 2.3 million Americans have the disorder.

ADPEAF is an extremely rare variant of epilepsy that usually develops between the ages of 8 and 25. People with epilepsy don't commonly report auditory hallucinations or sound distortions.

Doctors suspect that a region of the brain called the lateral temporal lobe is involved in the onset of the seizure.

Senior investigator Ruth Ottman, a professor of epidemiology at Columbia University in New York, had been studying a group of 2,000 families recruited through various epilepsy organizations, looking for types of epilepsy that were more likely to have a genetic factor.

From this large group, Ottman met a family in which 11 members had epilepsy, and were found to share a similar genetic marker on chromosome 10.

"We were able to get evidence that a rather large region of chromosome 10 must contain a gene that is raising risk for epilepsy in this family," says Ottman.

At that point, the researchers started to examine the family members' medical history. More than half had epileptic seizures that featured auditory hallucinations or distortions of sound as a prelude to their seizures. "The seizure activity in the brain was actually producing a clinical manifestation that involved sound," says Ottman.

"Some people hear, for example, the sound of helicopters or the sound of a machine, or a sound growing louder, or a whooshing sound or a thumping sound," she says. Others have described a ringing or humming noise in their ears or the sound of singing. "They know that a seizure is coming because they can hear these sounds."

Sometimes a follow-up seizure doesn't materialize, but it can progress to other types of seizures, including the full-body convulsions most commonly associated with epilepsy.

To narrow the search for the gene further, they turned to genetic analysis of other families with epilepsy, finding 28 potential genes before identifying mutations in the LGI1 gene in five families with ADPEAF. The mutations made the gene nonfunctional.

In mice, the researchers determined that the LGI1 gene was primarily active in neurons, specifically in the temporal lobes of the brain, confirming its link to ADPEAF.

Ottman says these findings open many new avenues for research, because unlike the eight previous genes linked to autosomal dominant forms of epilepsy, this gene is not involved in moving chemical signals in and out of brain cells.

The researchers suspect that the gene is normally active while the brain is developing, and that the mutation may change how brain cells called neurons migrate during development. "It's not a severe problem, because these people don't have any other [medical] problems other than their epilepsy," says Ottman.

Moreover, people with ADPEAF are often in remission or can control their seizures with medication.

If the gene's role in brain development can be understood, says Ottman, it could lead to the step in that growth that's crucial to developing epilepsy, which could point to ways to prevent the disorder.

"It really sets the stage for some highly focused experiments on the role of this molecule in brain cells in this region," Noebels says. The next step, he adds, will be to breed a strain of mice without the LGI1 gene and study the function of the animals' brains in the absence of the gene.

The ultimate goal is a therapy that would restore the function that the gene normally carries out, he says.

What To Do

For more information on genetics and epilepsy, check out these Web sites from Columbia University, the Harvard Mahoney Neuroscience Institute or the International League Against Epilepsy.

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