Single copy of Parkinson's-risk gene mutation may lead to earlier symptom onset

Mutations in a gene already known to play a role in causing an inherited form of Parkinson disease may also influence the age at which symptoms of the neurological disorder appear. While inheriting two abnormal copies of the parkin gene previously had been associated with the development of early-onset Parkinson's, a new study from a multi-institutional team led by Massachusetts General Hospital (MGH) researchers finds that even a single mutated copy of parkin reduces the age of onset of the disease. The findings appear in the June Archives of Neurology.

"This study reinforces the fact that there are multiple mechanisms behind Parkinson disease and will lead us to examine other pathways with which parkin interacts," says James Gusella, PhD, director of the MGH Center for Human Genetic Research, the study's senior author. The report is part of the larger GenePD project, an international collaborative study of siblings with Parkinson disease, which is based at Boston University Medical Center and led by Richard Myers, PhD.

Parkinson disease is a neurodegenerative disorder characterized by tremors, rigidity, difficulty walking and other symptoms. It is caused by the destruction of brain cells that produce the neurotransmitter dopamine and is the second most common neurodegenerative disorder. The condition's prevalence increases with age appearing in 1 percent of those over 60 and 4 to 5 percent of those over 85 but it can develop in much younger patients. While the cause of most cases of Parkinson's is unknown, there are rare, inherited forms. Five genes have been identified as increasing the risk for Parkinson's parkin mutations inherited from both parents being the most common genetic cause of early-onset disease but additional susceptibility genes are yet to be found.

Since finding new genes is a goal of the GenePD study, a preliminary step is to identify those whose familial Parkinson's can be attributed to one of the known gen

Contact: Sue McGreevey
Massachusetts General Hospital

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