- As is the case for mutations in LRRK2, a person need only inherit a mutation in the alpha-synuclein gene (SNCA, also known as PARK1 or PARK4) from one parent to be at substantial risk for Parkinson’s disease. The average age for disease onset in people with a disease-causing mutation in this gene is 46. The protein encoded by the alpha-synuclein gene is one of the main components of the protein aggregates found in brain cells of people with Parkinson’s disease.
- Mutations in parkin (PARK2), PINK1 (PARK6) and DJ1 (PARK7) are recessive, which means a person must inherit mutated copies of these genes from both parents in order to develop Parkinson’s (there are rare exceptions). Multiple mutations in each of these genes have been identified; some are extremely rare.
- Parkinson’s disease caused by mutations in parkin, PINK1 or DJ1 usually strikes at a young age. Parkin mutations most often lead to disease onset between the ages of 20 and 40, although some people are younger than 10 or older than 60 when they develop symptoms. PINK1 mutations usually cause Parkinson’s between the ages of 32 and 48. DJ1 mutations are associated with an age of onset between 20 and 40 years of age.
Michael J. Fox Foundation, the Parkinson’s Institute and patients from around the world partly because we want to give individuals with Parkinson’s access to their own genetic data. At the same time, we want to join the continuing quest for those genetic and environmental factors that underlie Parkinson’s disease by combining genetic data from our community with members’ responses to surveys about their health.By far the most common known genetic cause of Parkinson’s disease is the G2019S mutation, which occurs in a gene called LRRK2. While the average person has a 1-2% chance of developing Parkinson’s, the risk for someone with the G2019S mutation is much higher and increases with age. One recent study found that a person who inherits this mutation from either parent has a 28% chance of developing Parkinson’s by the age of 59, 51% by the age of 69 and 74% by the age of 79.Even though it is the most common known genetic cause of Parkinson’s disease, the G2019S mutation is responsible for only a small fraction of all cases worldwide – about one or two in a hundred. But in some ethnic groups it is a much more frequent cause of the condition. According to published research, up to 40% of people of North African Arab ancestry and 20% of Ashkenazi Jewish people with Parkinson’s have this mutation.Another mutation in the LRRK2 gene, referred to as G2385R, has been associated with Parkinson’s disease in several East Asian populations. Analyses of the combined results from several studies indicate that people who inherit this mutation from either parent are at two to three times greater odds of developing Parkinson’s than those who do not carry the mutation. Approximately 9% of Parkinson’s patients with Asian ancestry carry the G2385R mutation.(23andMe customers can find out if they carry the LRRK2 G2019S mutation in the Parkinson’s Disease Clinical Report. Customers can also find out if they carry the G2385R mutation using the Parkinson’s Disease: Preliminary Research Report.)Although people who have at least one copy of the LRRK2 G2019S or G2385R mutation have an increased risk of Parkinson’s disease, a substantial proportion of people with these mutations never develop the disease. Very little is known about the function of the protein made by the LRRK2 gene, and no one knows why many people who carry mutations in this gene don’t develop Parkinson’s disease. Adding to the mystery, among those with these mutations who do develop Parkinson’s, not all have the same symptoms. Interactions of these mutations with unknown environmental factors may be part of the explanation. Continuing research into these gene-environment interactions could yield valuable clues into the causes of Parkinson’s generally.Mutations in several other genes have also been associated with Parkinson’s disease, but these are extremely rare. Many have been found only in one or two families. 23andMe is not able to detect most of these rare mutations.Other Parkinson’s mutations: