Separate published studies found two mutations on a gene that has already been implicated in the disease.
Researchers at the Mayo Clinic site in Florida identified two mutations associated with Parkinson’s disease on the leucine-rich repeat kinase 2 (LRRK2) gene. They suggest that this discovery supports the hypothesis that even what appears to be sporadic cases of Parkinson’s are actually inherited.
The findings, which are reported in two separate journals, brings the total number of disease-related mutations on this gene to seven.
In the study appearing on April 16 on the online edition of the Annals of Neurology, scientists studied 1,079 ethnic Han Chinese diagnosed with Parkinson’s disease; 44 patients reported a family history of the disease. These patients were compared with 907 matched Han Chinese who did not have Parkinson’s. Results showed that the R1628P variant on LRRK2 was approximately twice as frequent in patients as in the control population. Further research suggested that the R1628P carriers were related to a single common founder that dated from about 2,500 years ago.
Researchers in the second study, published on April 15 in Neurology, collected genetic information from discrete populations of people representing three continents who had previously been found to be carriers of the R1441C mutation, also on LRRK2. They demonstrated that R1441C increases risk of the disease by more than 10-fold.
These patients all developed disease that mimicked the typical, late-onset version normally seen in nonfamilial, sporadic Parkinson’s disease, report the investigators. They believe the same disease-causing mutation occurred independently on several occasions. Most patients, however, seem to originate from two different founders.
In Parkinson’s, it seems that genetic risk factors are passed down through the population for hundreds or thousands of years, according to the research team. This adds up to substantial susceptibility within a single individual and with some possible environmental influences, can result in disease, explains Mayo Clinic neuroscientist Owen A. Ross, Ph.D., first author on the Annals of Neurology paper.
Even in sporadic disease, familial genes are inherited, but symptoms may skip some generations, making the disease appear sporadic, continues Kristoffer Haugarvoll, M.D., a visiting scientist at Mayo Clinic and lead author of the study in Neurology.