Gene mutation causes Parkinson's disease in some families

Oct 22 2004

An international research team, led by scientists at the National Institute on Aging (NIA), has discovered a gene, which when mutated, causes Parkinson's disease in some families.

Although Parkinson's disease is usually not inherited, the discovery of this gene and further study of how it works could open up new avenues of research for preventing or delaying the onset of the disease. In research, the study of rare familial forms of a disease has often led to major insights into the pathogenesis of more common forms.

The finding was published online by Neuron at noon ET on October 22, 2004. The collaborative work was spearheaded by Andrew Singleton, Ph.D., at the NIA, Jordi Perez-Tur of the Institut de Biomedicina de Valencia in Spain, and Nick W. Wood of the Institute of Neurology in London. The NIA is a part of the National Institutes of Health (NIH) at the U.S. Department of Health and Human Services.

"Parkinson's disease has a devastating impact upon individuals," says Elias A. Zerhouni, M.D., Director of the NIH. "This finding provides scientists with important new information about genetic mutations that underlie this disease, giving us new understanding about molecular mechanisms. Ultimately, this research will help in the development of targeted interventions that could actually alter the course of this disabling disease."

The gene, PARK8, encodes a protein named dardarin by the researchers, from the Basque word dardara, which means tremor, a major symptom of Parkinson's disease. It was isolated on chromosome 12 by investigators who studied five families with a history of Parkinson's disease who lived in the Basque region of Spain and in England. First, the group identified a small region of the chromosome 12 shared by all of the Basque families and then systematically assessed each gene in this region for mutations that might cause disease. The investigators identified two mutations in the same gene, one associated with Parkinson's disease in the Basque families and the other which was linked to the disease in the English family.

"The discovery of this cluster of Basque families with Parkinson's disease helped us to narrow the genetic region we were interested in," Dr. Singleton says. Once the genes for a particular complex trait or disease, such as Parkinson's, are identified within "founder" populations, such as the Basques, researchers can use this information to isolate interacting genes and assess their importance in more genetically diverse cultures. Worldwide, the researchers have identified another 8 to 11 families suspected of having similar mutations, including at least one in the United States.

The investigators were brought together by Dr. Singleton to pool resources and speed the search. "This was a true collaborative venture that we couldn't have done working separately," he says.

Dr. Singleton points out that other groups are working on isolating additional genes involved in the disease. There are likely other mutations in the Parkinson's disease population, he says, noting that the new data suggest that there will be mutations in typical sporadic Parkinson's disease cases in addition to those who have a family history of the disease.

About 50,000 Americans are diagnosed with Parkinson's disease each year. The disease occurs when certain nerve cells die or become impaired and can no longer produce dopamine. Without it, individuals can develop tremor or trembling in hands, arms, legs, jaw, and face; rigidity or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability or impaired balance and coordination. Patients may also have difficulty walking, talking, or completing other simple tasks. The disease is both chronic and progressive. Parkinson's disease is not usually inherited, but incidence of the disease increases with age, with an average onset at about 60 years.