Genetic mutation sheds light on Parkinson's origins

Neurologists have isolated a gene mutation responsible for both familial and sporadic forms of Parkinson's disease.

Baylor College of Medicine participated in the multi-center study. Results are published in the Jan. 29 print edition of The Lancet.

"This represents the most significant gene mutation in patients of Parkinson's disease," said Dr. Joseph Jankovic, professor of neurology and director of BCM's Parkinson's Disease Center and Movement Disorders Clinic. "Because it is such a frequent mutation, it will allow us to test for this genetic abnormality in a population of patients with Parkinson's disease, which will have obvious implications for genetic counseling and confirming the diagnosis."

The study, conducted at 59 sites, was funded by the National Institutes of Health. It included genetic analyses of 767 Parkinson's patients from 358 families and determined that a single mutation in the LRRK2 gene is responsible for at least 5 percent of all familial cases of the disease. Jankovic, who served as principal investigator at the BCM test site, said that clearly more than 5 percent of all Parkinson's patients - not just those with family histories of the disorder - may have the mutant LRRK2 gene.

"We strongly suspect that a much larger population of patients with Parkinson's disease will have mutations of this particular gene," Jankovic said. "Since this gene mutation is found even in sporadic cases, that by itself proves even patients who do not have family history probably have a genetic form of Parkinson's."

The robust sample of patients tested in the study allowed researchers to examine changes in their DNA that do not ordinarily occur in the general population, showing that genetic variations can indeed cause Parkinson's. Moreover, Jankovic points out that this discovery represents only one out of potentially many mutations of the LRRK2 gene.

"Conventional wisdom states that only a small percentage of patients with Parkinson's have a genetic predisposition, but this study suggests that the percentage is much higher," Jankovic said. "We have not even seen the tip of the iceberg, and I think we will find other genes that are responsible for other forms of Parkinson's."

Since genetic screening plays a vital role not only in the confirmation of diagnoses but also in early detection of disorders like Parkinson's, treatment options could be made more effective by being implemented earlier in addition to better understanding the pathogenesis.

"The discovery of genes that cause Parkinson's will hopefully lead us to a better understanding of the function of proteins produced by the gene that are important in the mechanism of cell death in Parkinson's," Jankovic said. "By understanding the mechanism by which cells die due to abnormal function of these proteins, we can hopefully design better therapeutic strategies."