Research shows Parkinson's is primarily an inherited genetic disorder

Washington, April 17 : Mayo Clinic scientists have found in two international studies that Parkinson's disease is primarily an inherited genetic disorder.

The researchers say that their findings are based on various mutations observed during the two studies.

According to them, the new research overturns common beliefs that the neurodegenerative disease mostly occurs in a random fashion or due to undetermined environmental factors.

In all, the research brings the total number of disease-related mutations in an as yet poorly understood gene, known as leucine-rich repeat kinase 2 (LRRK2), to seven.

All these mutations are linked to typical, late onset development of Parkinson's disease in people around the world, say the researchers.

In a study report, appearing in the online edition of the Annals of Neurology, the researchers have revealed that one mutation (R1628P) doubles the risk of Parkinson's disease in ethnic Chinese. This mutation arose from a single individual in the Han Chinese population about 2,500 years ago and has since spread through generations of descendants, wherever they live.

"The picture that is emerging of Parkinson's disease is one in which genetic risk factors, passed down through the population for hundreds or thousands of years, add up to substantial susceptibility within a single individual, and, with some possible environmental influences, can result in disease," says Mayo Clinic neuroscientist Dr. Owen A. Ross, first author on the study.

"These types of mutations are important because the goal of this research is to be able to screen people who are most at risk because of their genetic profiles, and design therapies that interfere with the disease process," Dr. Ross adds.

In another study paper, published in the journal Neurology, the researchers say that a very rare mutation (R1441C), found in 20 families on three continents, leads to a 10-fold increased risk.

"Parkinson's disease is fascinating to study because we can now roughly trace when and where mutations occur, and how they travel through offspring and in populations," says lead author Dr. Kristoffer Haugarvoll, a visiting scientist at Mayo Clinic.

"It also shows us that disease that appears to be the same in the majority of patients can originate from different genetic mutations - either genes that increase risk substantially, or by several risk factors, genetic and environmental, that each have minor but additive effects," he adds.

The study led to the identification of 33 affected and 15 unaffected R1441C mutations from 20 families, including four patients with no family history of Parkinsonism.

Haugarvoll says that all those patients developed disease that mimicked the typical, late onset disease normally seen in non-familial, sporadic Parkinson's disease.

He says the region of R1441C appears to be "a hotspot for mutation events" because other mutations occur in this general area.

What is most interesting, he says, is that "even though there are familial mutations in different locations of the gene, it produces the same effect, the same disease."

"It seems like mutations are occurring in a few founders, and that these founders have a lot of offspring over generations that carry the mutation. Even in sporadic disease, then, familial genes are inherited but symptoms may skip some generations, making the disease appear sporadic" Dr. Haugarvoll says.

ANI