A Novel Gene is Causing Restless Legs Syndrome

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In 2005, a woman who had trouble sleeping asked Siong-Chi Lin, M.D., for help. Dr. Lin, a sleep disorders specialist at the Mayo Clinic campus in Florida, diagnosed restless legs syndrome. This common neurologic disorder interrupts sleep because of unpleasant sensations in the legs at rest, particularly in the evening, that are temporarily relieved by movement.

Restless legs syndrome affects between 5 and 11 percent of the population in North America and Europe, says Dr. Lin. The cause appears to be many clinical factors, such as iron deficiency, but it has a strong genetic component as well. "In most people, it is likely due to many different causes, but genes are very likely the most important factor in affected families," he says.

Medications, particularly agents that increase transmission of dopamine in brain neurons, are effective in a number of people and worked for his new patient, says Dr. Lin. "The syndrome may appear as a nuisance for most people, however it can also seriously affect some people's quality of life," he says.

Dr. Lin's patient told him that a number of of her relatives also have the same trouble sleeping - difficulties she could trace back through her ancestry.

With the patient's approval, that information was relayed to "gene hunters" in Mayo Clinic's neurosciences department. These researchers have established an international reputation for their ability to find the genetic roots of rare, as well as common, neurological disorders. Dr. Lin accompanied researchers to Indiana, the hub of the extended family, which is thought to beof English descent, to interview dozens of individuals spanning multiple generations. They observed that 30 relatives were affected by restless legs syndrome, and discovered that almost three times as a number of females had the condition in comparison to males.

Now, the scientists are reporting in the recent issue of Mayo Clinic Proceedings that the restless legs syndrome found in this family is likely due to a gene mutation that has never been associated with the disorder.

To date, five loci, or areas on the genome, have been associated with restless legs syndrome in other families around the world, but this family does not have any of those mutations.

"That means this family likely has a novel gene that is causing the disease," says the study's lead investigator, Carles Vilariño-Güell, Ph.D., a neuroscientist at Mayo Clinic's campus in Jacksonville. The scientists have still not pinpointed the culprit gene, but say they are getting close.

This study is important, Dr. Vilariño-Güell says, because this family is one of the largest with restless legs syndrome ever studied, and the disorder spans multiple generations. Therefore, the gene associated with the syndrome is widespread among the affected relatives, increasing the chances that the scientists will soon zero in on the gene responsible.

"With so a number of people in this family affected by the syndrome, we have a lot of power to find the gene mutation causing disease," he says.

Once a gene is discovered, scientists can investigate its normal function and the mutation's effect, and then can "try to overcome that problem with drug treatment," he says. They can also trace the molecular route from the gene mutation to the disorder, and see if the other loci associated with the syndrome lie along this pathway. So far, no one has found a definitive link between restless legs syndrome and a specific gene mutation, but large families hold the clues for these discoveries, says Dr. Vilariño-Güell.

Co-authors of the study include Matthew Farrer, Ph.D., and Zbigniew Wszolek, M.D.


Posted by: Daniel    Source