Ya-Ping Yan1, Cong-Ying Xu2, Lu-Yan Gu1, Bo Zhang3, Ting Shen1, Ting Gao1, Jun Tian1, Jia-Li Pu1, Xin-Zhen Yin1, Bao-Rong Zhang1, Guo-Hua Zhao1,4. 1. Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 2. Department of Neurology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China. 3. Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 4. Department of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract
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.
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.
Authors: Félix Javier Jiménez-Jiménez; Hortensia Alonso-Navarro; Elena García-Martín; Ignacio Álvarez; Pau Pastor; José A G Agúndez Journal: Pharmaceuticals (Basel) Date: 2021-05-27