What this means

LRRK2 encodes a kinase involved in vesicle trafficking and autophagy. The G2019S variant is the most common Mendelian cause of Parkinson's disease, but penetrance is incomplete: estimates put the lifetime risk for carriers somewhere between 25 and 75 percent depending on the population studied. Most carriers in family-based studies are unaffected at the time of recruitment.

LRRK2 makes an enzyme involved in how cells move things around and clean themselves up. The G2019S DNA change is the most common single inherited DNA change known to cause Parkinson's disease — but it doesn't always lead to the disease. Estimates of the lifetime chance for people with this DNA change range from about 25 to 75 percent depending on which group has been studied. Most people with it in family studies don't have Parkinson's when they're first looked at.

Caveats

• Penetrance estimates vary widely depending on whether the study sample is family-ascertained or population-based.
• Even confirmed carriers typically develop Parkinson's late in life, if at all.
• Many LRRK2 inhibitor trials are underway; carriers may want to follow the literature.
• Genetic counselling is recommended before sharing this result with relatives.

Populations

• Most common in Ashkenazi Jewish, North African Berber, and some European populations

References

• Healy et al. — Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease (Lancet Neurology, 2008)
• Goldwurm et al. — Evaluation of LRRK2 G2019S penetrance (Neurology, 2011)