Purpose of review: This review summarizes some key findings of the past few years on the genetics of the two common movement disorders Parkinson's disease and essential tremor.
Recent findings: Within the last two years, genome-wide association (GWA) analyses have revealed a number of novel low-risk susceptibility variants for Parkinson's disease, among them HLA-DRB5, BST1, ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R) and have confirmed LINGO1 as risk factor for essential tremor. The identification of copy number variations in the Parkin gene in healthy control individuals suggests no major role of these variations in late onset Parkinson's disease. Drosophila studies on Parkin and Pink1 have uncovered a role in the mitochondrial quality control pathway in the pathogenesis of the disease. LRRK2 has been found to interact with the microRNAs processing protein Argonaut, thereby affecting protein translation. Notably, despite the high familial risk for essential tremor no high-risk gene has been found to date. The possibility of a nonmendelian transmission in some cases is discussed.
Summary: GWA studies and positional cloning approaches have led to the identification of a number of risk genes for Parkinson's disease, which give novel insights into pathogenic pathways of the disease. In contrast, our knowledge of the genetics of essential tremor is scarce. Except for LINGO1, no other risk gene has so far been identified. New technologies such as next generation high throughput sequencing might help to identify more risk genes.