| Researchers Discover Gene Mutations for Parkinson's
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 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
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,”
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.
The NIA conducts and supports research on aging and age-related
diseases, including neurodegenerative diseases such as Parkinson’s
disease. For more information on NIA’s research programs in
this area, visit its Alzheimer’s Disease Education and Referral
(ADEAR) Center website at www.alzheimers.org
, or call 1-800-438-4380. The National Institute of Neurological
Disorders and Stroke (NINDS), also part of the NIH, conducts research
on Parkinson’s disease and other neurological disorders and
provides information to the public and to patients on the disease.
For more information on Parkinson’s disease specifically,
please visit the NINDS website at www.ninds.nih.gov