Genetic analysis of PITX3 variants in patients with essential tremor
Essential tremor (ET), underlying mechanism of which remains poorly understood, is one of the most common age‐related movement disorders. The worldwide prevalence of ET is estimated to be 0.9%, increasing to 4.6% in individuals ≥65 years 1. ET is strongly inherited but the mainly disease‐causing gene is still not identified. At least eight disease‐causing loci for familial ET were identified: ETM1 (3q13, MIM 190300), ETM2 (2p24.1, MIM 602134), ETM3 (6p23, MIM 611456), ETM4 (16p11.2, MIM 137070), and four loci (on 2p13.1, 1p13.3, 11q14.1, and 17q23.3), which have not been recruited in Online Mendelian Inheritance in Man (OMIM) currently. Rare mutations in the fused in sarcoma gene (FUS, MIM 137070), the HtrA serine peptidase 2 gene (HTRA2, MIM 606441), the sortilin 1 gene (SORT1, MIM 602458), the teneurin transmembrane protein 4 gene (TENM4, MIM 610084), and the sodium channel voltage gated type IV alpha subunit gene (SCN4A, MIM 603967) were found in a few ET families. Additionally, variations in the alpha‐synuclein gene (SNCA), the dopamine receptor D3 gene (DRD3), the leucine‐rich repeat and Ig domain containing 1 gene (LINGO1), LINGO2, the solute carrier family 1 (glial high affinity glutamate transporter) member 2 gene (SLC1A2), the heme oxygenase 1 gene (HMOX1), and HMOX2 have also been reported to be associated with ET susceptibility, although more replication studies are warranted 2.
Given that the clinical and pathological overlaps were observed between ET and Parkinson's disease (PD), analyses of gene variants known to confer the risk for PD may provide insight into the genetics of ET. Intriguingly, variants rs3758549 and rs4919621 in the paired‐like homeodomain transcription factor 3 gene (PITX3, MIM 602669) were reported to be associated with PD susceptibility 4. This study was therefore intended to explore whether PITX3 variants (rs3758549 and rs4919621) are associated with ET in a large sample of Chinese Han ET patients from mainland China.