Parkinsonism, dementia and glucocerebrosidase mutations
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A number of genes are now known to cause Parkinson’s disease (PD) and include Parkin, PTEN-induced putative kinase 1 (PINK1), DJ-1, ATP13A2, SNCA and leusine-rich repeat kinase 2 (LRRK2). The LRRK2 mutations are the most common and thought to be responsible for 5 % of familial and 3 % of all sporadic cases. However, almost two decades ago clinicians began to report Parkinsonian features in patients with Gaucher’s disease, an autosomal recessive lysosomal storage disease with a clear and uniform genetic aetiology caused by mutations in the glucocerebrosidase (GBA) gene located on the long arm of chromosome 1. As a result, a number of subsequent studies have investigated the association and potential causative role that GBA mutations may play in PD, eventually determining that GBAmutations represent a common risk factor for developing not only PD but also dementia with Lewy bodies (DLB). Intriguingly the common histopathological hallmark of both these disorders are Lewy bodies, which...