Researchers say the mutation on the LRRK2 gene is responsible for 5 percent of inherited Parkinson's disease cases.
Tatiana Foroud, Ph.D., associate professor of medical and molecular genetics at Indiana University School of Medicine and principal investigator on the multi-site study, said the discovery has a broad implication for genetic screening for the disease.
"Our results suggest that the mutation we have studied is the most common cause of Parkinson's disease identified to date," said Dr. Foroud. "While a great deal of work remains to be done, it is clear that any future genetic testing for Parkinson's disease must include studies of the LRRK2 gene."
The patients in the Indiana University study who had the mutation had longer disease duration but less severe symptoms when they were participating in the trial. That suggests that the mutation may be associated with slower disease progression, said Dr. Foroud.
The Indiana University paper published in The Lancet is one of three Parkinson's studies to appear in the upcoming edition. The second study is by Nicholas W. Wood, M.D., of the Institute of Neurology in London. The third paper is by Vincenzo Bonifati, M.D., Ph.D., of Erasmus MC in Rotterdam, Netherlands.
The studies will be available in the Jan. 18 online edition of The Lancet and the Jan. 29 edition of the journal.
The IU study focused on 767 Parkinson's disease patients from 358 families. The patients were recruited by specialists from 59 medical centers associated with the Parkinson Study Group, a non-profit, cooperative group of Parkinson's disease experts from the United States, Canada and Puerto Rico.
The molecular studies were performed at Cincinnati Children's Hospital Medical Center under the direction of William C. Nichols, Ph.D., the paper's first author. This study found that 5 percent of the patients carried the same LRRK2 mutation.
The Wood report focuses on Parkinson's disease patients without a known family history of the disease. Dr. Wood found the same LRRK2 gene mutation in eight of 482 study participants.
The Bonifati study identified the same LRRK2 gene mutation as the Cincinnati Children's study. Bonifati found the mutation in four of 61 families with a history of Parkinson's disease.
"When we began, we really didn't know how frequent this mutation in the LRRK2 gene would be, but to find the same single mutation in the genome in Parkinson's patients is pretty dramatic," said Dr. Nichols, a geneticist at the Cincinnati medical center.
The LRRK2 gene, which is on a region of chromosome 12 called PARK8, is one of five Parkinson's disease genes in which mutations have been identified. LRRK2 was isolated by Andrew Singleton, Ph.D., of the National Institute on Aging at the National Institutes of Health, during a study of five families with a history of Parkinson's disease.
Parkinson's disease is a progressive disorder caused by the degeneration of nerve cells in the portion of the brain that controls movement. When certain nerve cells die or become impaired they no longer produce dopamine, a brain chemical that controls tremors, rigidity, stiffness of limbs, impairment of coordination and other symptoms associated with Parkinson's disease. For years it was believed that environmental factors were the primary cause of Parkinson's disease. It wasn't until 1997 that the first gene associated with the disease was identified.
The multi-site study under the direction of Dr. Foroud is an $8 million grant from the National Institute of Neurological Disorders and Stroke designed to identify the genes causing Parkinson's disease.
Families with at least two living members affected by Parkinson's disease may obtain more information about the IU study at http://progeni.iu.edu, or they may call 888-830-6299 to enroll.
(To speak with Dr. Nichols, contact Amy Reyes at 513-636-9684, or amy.reyes@cchmc.org. To speak with Dr. Singleton, contact Doug Dollemore at 301-496-1752, or dollemod@nia.nih.gov. During Monday's holiday, he can be reached at 301-980-8307.)
Journal
The Lancet