Two 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 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.

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.

“ 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, 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. ”

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 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, researchers 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.

Parkinson’s disease, which affects at least 500,000 Americans. About 50,000 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 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 study has been published in Lancet.

Source: NIH, 2005


XagenaMedicine2005