Genetic testing of FUS, HTRA2, and TENM4 genes in Chinese patients with essential tremor

• Published in: CNS neuroscience & therapeutics Vol. 26; no. 8; pp. 837 - 841
• Main Authors: Yan, Ya‐Ping, Xu, Cong‐Ying, Gu, Lu‐Yan, Zhang, Bo, Shen, Ting, Gao, Ting, Tian, Jun, Pu, Jia‐Li, Yin, Xin‐Zhen, Zhang, Bao‐Rong, Zhao, Guo‐Hua
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2020; John Wiley and Sons Inc
• Subjects: essential tremor; Etiology; Family medical history; FUS; FUS protein; Genes; genetic analysis; Genetic screening; Genome-wide association studies; Genomes; HTRA2; Linkage analysis; Movement disorders; Mutation; Original; Parkinson's disease; Polymorphism; Single-nucleotide polymorphism; Studies; TENM4; Tremor; Tremor (Muscular contraction); HTRA2; essential tremor; genetic analysis; TENM4; FUS
• ISSN: 1755-5930; 1755-5949; 1755-5949
• DOI: 10.1111/cns.13305

Introduction Essential tremor (ET) is one of the most prevalent movement disorders. The genetic etiology of ET has not been well defined although a significant proportion (≥50%) are familial cases. Linkage analysis and genome‐wide association studies (GWASs) have identified several risk variants. In recent years, whole‐exome sequencing of ET has revealed several specific causal variants in FUS (p.Q290X), HTRA2 (p.G399S), and TENM4 (c.4324 G>A, c.4100C>A, and c.3412G>A) genes. Objective To investigate the genetic contribution of these three genes to ET, the protein‐coding sequences of FUS, HTRA2, and TENM4 were analyzed in a total of 238 ET patients and 272 controls from eastern China using direct Sanger sequencing. Results We identified two synonymous coding single nucleotide polymorphisms (SNPs), rs741810 and rs1052352 in FUS, and three previously reported synonymous SNPs, rs11237621, rs689369, and rs2277277 in TENM4. No nonsynonymous exonic variants were identified in these subjects. We found that the frequency of the rs1052352C allele was significantly higher (P = .001) in the ET group than in the control group. Conclusion Overall, our findings suggest that rs1052352 of FUS might contribute to ET risk in Chinese population.