We analyzed in ET Spanish families three single nucleotide polymorphisms (SNPs): DRD3rs6280, SLC1A2 rs3794087, and MAPT rs1052553) previously related to an increased risk for developing the disease.
Recently, in a large ET family (FET1) from Quebec, a non-sense mutation (p.Q290X) in the amyotrophic lateral sclerosis (ALS) gene fused in sarcoma/translated in liposarcoma (FUS/TLS) was identified by exome sequencing.
We did not find a significant association of the DRD3 variant with ET nor linkage to the DRD3 receptor in German, Danish and French ET patients and families, suggesting that it is unlikely to be a causal factor for ET.
These results suggest that DRD3 genotype and the variant DRD3Gly allelic variant is associated with the risk for and age at onset of ET, and with the risk for voice tremor, in Caucasian Spanish people.
Two genetic loci have been identified in autosomal dominant (AD) ET and polymorphisms in the DRD3 and HS1-BP3 genes have been proposed as the possible susceptibility factors for ET.
The gain-of-function produced by the Gly-9 variant may explain why drugs active against tremor in Parkinson's disease (PD) are usually not effective in the treatment of ET and suggests that DRD3 partial agonists or antagonists should be considered as novel therapeutic options for patients with ET.
We now report evidence for linkage to the ETM locus in three additional, unrelated American families with ET and exclude the FET1 locus in these families.