Scientists Detect Probable Genetic Cause of Some Parkinson's Disease Cases
Two new studies strongly suggest that a mutation in a recently
discovered gene is the most common genetic cause of Parkinson’s
disease identified to date. The discovery by an international research
team provides fresh evidence that genetics may contribute to the
development of some cases of Parkinson’s disease. The findings
could lead to the development of a genetic test to detect the mutation
in individuals at risk. The research team includes investigators
at the National Institute on Aging (NIA) and scientists supported
by the National Institute of Neurological Disorders and Stroke
(NINDS).
Parkinson’s disease, which affects at least 500,000 Americans,
is a progressive neurologic disorder that is caused by the degeneration
of nerve cells in the portion of the brain that controls movement.
Scientists have long suspected genetics play a role in the onset
of the disease. In these studies, the investigators found that
a mutation in the gene LRRK2 appears to occur in at least one
of every 60 people who have the disease. Overall, the mutation
could be responsible for up to 5 percent of Parkinson’s
disease in people with a family history of the disorder and may
account for 1½ to 2 percent of cases in individuals who
do not have a family history of the disease. The researchers found
a mutation in one copy of the gene can lead to the disease. The
findings* were published online by Lancet at 6:30 p.m. ET on January
17, 2004.
“Among the forms of Parkinson’s disease that are
genetic in origin, this gene mutation causes more cases of Parkinson’s
disease than any other gene discovered to date,” says Andrew
Singleton, Ph.D., chief of the Molecular Genetics Unit in the
NIA’s Laboratory of Neurogenetics. “Knowing that this
mutation is not only important in familial forms of disease, but
in typical sporadic disease, where there is no strong family history,
could lead to earlier detection of Parkinson’s disease.
Further study of how this gene works also might help scientists
identify
new treatments.”
In addition to Dr. Singleton, the collaborative work was spearheaded
by William C. Nichols, Ph.D., of Cincinnati Children’s Hospital,
Tatiana Foroud, Ph.D., of Indiana University Medical
Center, Indianapolis, and Nicholas W. Wood, M.D., of the Institute
of Neurology in London. The NIA and the NINDS are part of the
National Institutes of Health (NIH) at the U.S. Department of
Health and Human Services.
Singleton and his colleagues recently discovered LRRK2, a gene
that 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 a region of chromosome
12 called PARK8 by investigators who studied five families with
a history of Parkinson’s disease who lived in the Basque
region of Spain and in England.
In these new studies, the researchers sought to determine the
prevalence of the genetic mutation in other families and individuals
being studied by the Parkinson’s Study Group with NINDS
support. In an analysis of 358 families with a history of Parkinson’s
disease, for instance, the investigators found that 34 of the
767 people who had inherited the disease had at least one copy
of the mutated gene. Similarly, the team detected one copy of
the mutation in 8 of 482 people with Parkinson’s disease,
but who didn’t report a family history of the disease. The
Parkinson’s Study Group is a non-profit, cooperative group
of Parkinson’s disease experts from 59 medical centers in
the United States and Canada who are dedicated to improving treatment
for people affected by Parkinson’s disease.
“NINDS is pleased to have supported the collection of this
large group of families and sibling pairs, which is proving to
be an invaluable resource for these studies, says Diane Murphy,
Ph.D., a program director at NINDS. “Because the prevalence
of this mutation is 5 percent in families with a history of the
disease and it is relatively common even among those without a
family history, it’s possible that detecting this mutation
will help identify people at increased risk for Parkinson’s
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, a brain signaling
chemical (neurotransmitter). 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. 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 link to http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_research.htm.
*Copies of the studies will be made available to the media on
January 17. To request copies, journalists should email pressoffice@lancet.com.
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