Three studies published online by The Lancet today identify a single gene mutation as the cause of around one in 25 cases of Parkinson’s disease worldwide. The studies suggest that the mutation, in a recently discovered gene called LRRK2, causes around 5% of inherited Parkinson’s cases and around 2% of isolated cases. Screening for the new mutation is likely to become a component of genetic testing for Parkinson’s disease in the near future.
Parkinson’s is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting more than 1% of individuals after the age of 65 years. It is characterised by resting tremor, slowness of movement, muscle rigidity, postural instability and impaired balance and coordination.
Vincenzo Bonifati (Erasmus Medical Centre, Rotterdam, Netherlands) and colleagues analysed the LRRK2 gene in 61 families with Parkinson’s disease. The investigators found that individuals in 4 unrelated families had inherited one copy of the mutation. Their findings indicate that this mutation is associated with the hereditary form of the disease.
Dr Bonifati comments: “This is a significant step forward in our understanding of the causes and mechanisms of Parkinson’s disease, with implications for both the scientific and clinical communities. The main challenge is now to try and understand how this and the other PDassociated LRRK2 mutations lead to neurodegeneration and disease, in order to design novel therapeutic and preventive strategies.
“From the genetic standpoint, the presence of the same mutation associated with the disease in patients from several different populations is intriguing. This raises the question of whether the mutation originated independently in the different cases and families, or if it was transmitted from a single common ancestor. Future genetic studies will address this issue; however, if it comes from a common ancestor, this mutation must be very ancient.”
Nicholas Wood (National Hospital for Neurology and Neurosurgery, London, UK) and colleagues analysed the LRRK2 gene in 482 Parkinson’s patients without a family history of the disease. The investigators found that the mutation was present in 8 patients; implicating the mutation in sporadic as well as inherited forms of the disease.