Parkinson's Disease

What do we know about heredity and Parkinson's disease?

Parkinson's disease (PD) is a neurological condition that typically causes tremor and/or stiffness in movement. The condition affects about 1 to 2 percent of people over the age of 60 years and the chance of developing PD increases as we age. Most people affected with PD are not aware of any relatives with the condition but in a number of families, there is a family history. When three or more people are affected in a family, especially if they are diagnosed at an early age (under 50 years) we suspect that there may be a gene making this family more likely to develop the condition.

What genes are linked to Parkinson's disease?

In 1997, we studied a large family that came from a small town in Southern Italy in which PD was inherited from parent to child (dominant inheritance). We found the gene that caused their inherited Parkinson's Disease and it coded for a protein called alpha-synuclein. If one studies the brains of people with PD after they die, one can see tiny little accumulations of protein called Lewy Bodies (named after the doctor who first found them). Research has shown that there is a large amount of alpha-synuclein protein in the Lewy Bodies of people who have non-inherited PD as well as in the brains of people who have inherited PD. This immediately told us that alpha-synuclein played an important role in all forms of PD and we are still doing a lot of research to better understand this role.

Since 1997 four other genes have been found and they have been named parkin, DJ1, PINK1, and LRRK2. The first three genes were found in affected individuals who had siblings with the condition but whose parents did not have Parkinson's disease (recessive inheritance). There is some research to suggest that these genes may also be involved in early-onset PD (diagnosed before the age of 30) or in dominantly inherited PD but it is too early yet to be certain. The most recently discovered gene (LRRK2) has been reported in families with dominant inheritance. Changes in this gene may account for 5-10% of dominantly inherited Parkinson’s disease

What determines who gets Parkinson's disease?

In most cases inheriting a non-working copy of a single gene will not cause someone to develop Parkinson's disease. We believe that many other complicating factors such as additional genes and environmental factors determine who will get the condition, when they get it and how it affects them. In the families we have studied, some people who inherit the gene develop the condition and others live their entire lives without showing any symptoms. There is a lot of research on genes and the environment that is attempting to understand how all these factors interact.

Genetic Testing in Parkinson's Disease

Genetic testing has recently become available for the parkin and PINK1 genes. Parkin is a large gene and testing is difficult. At the current stage of understanding, testing is likely to give a meaningful result only for people who develop the condition before the age of 30 years. Pink1 appears to be a rare cause of inherited Parkinson’s disease. A small percentage (~2 percent) of those developing the condition at an early age appear to carry mutations in the PINK1 gene.