Is Parkinson’s Hereditary?

Parkinson’s disease may be either hereditary, meaning it is caused by genetic factors, or sporadic, meaning it iscaused by environmental factors. In most cases, Parkinson’s is not hereditary nor directly inherited, and only 15 to 25 percent of Parkinson’s patients have a family history. In large population studies, researchers found that those with a family history of Parkinson’s have a 4 to 9 percent higher risk of developing disease than the general population.

Genes linked to the development of Parkinson’s are classified as either “‘causal genes” or “associated genes.”

Causal genes

Causal genes are those which carry mutations that, when inherited, cause the disease. Parkinson’s caused by these mutations is very rare, accounting for only 1 or 2 percent of all patients. One example of a causal gene is SNCA, which encodes a protein called alpha-synuclein. At least five mutations of SNCA have been found to cause Parkinson’s. These mutations can be inherited and directly cause the disease.

The “Iowa kindred” or “Spellman-Muenter kindred” is a large family in Iowa. Researchers traced 200 members of this family with and without Parkinson’s and analyzed their entire genome to identify the genes associated with the disease. They discovered that mutations in the SNCA gene coding for alpha-synuclein was the causal gene for Parkinson’s in this family. Normally, SNCA is located on chromosome 4 as a single copy. However, members of this family carried three copies of the gene that caused them to develop the disease at a young age.

Associated genes

Mutations in associated genes do not directly cause Parkinson’s, but increase the risk of developing it. A person may have mutations in associated genes and never get Parkinson’s, but is more likely to develop it. The combined effect of associated genes and environmental factors may trigger the development of Parkinson’s.

Genes associated with Parkinson’s disease include PRKN, which codes for the parkin protein;,PINK1, which codes for a protein found in the heart and skeletal muscles; LRRK2, which codes for a brain protein called dardarin; and PARK7, which codes for a brain protein called DJ-1.

Mutations in certain genes, including GBA (which codes for an enzyme called glucocerebrosidase) and UCHL1 (which codes for an esterase enzyme), also appear to increase the risk of developing Parkinson’s.

Mutations in the LRRK2 gene are common in people of North African, Basque, Portuguese, and Ashkenazi Jewish descent, but occur in almost all ethnic groups. Some people with LRRK2 mutations develop Parkinson’s disease as young as in their 30s while others develop the disease in their 80s, and others never develop it. There is great variability in the mutations that occur in the LRRK2 gene and the effects that these mutations have on the individual. Some people with LRRK2 gene mutations develop dementia, while others develop a form of Parkinson’s disease that shares features with amyotrophic lateral sclerosis (ALS). This variability, where some people develop certain disease features while others are protected, may provide clues about the underlying cause of Parkinson’s disease.

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