Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Neurology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.
CNS Neurosci Ther. 2020 Aug;26(8):837-841. doi: 10.1111/cns.13305. Epub 2020 Mar 20.
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.
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.
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.
Overall, our findings suggest that rs1052352 of FUS might contribute to ET risk in Chinese population.
特发性震颤（ET）是最常见的运动障碍之一。尽管很大一部分（≥50%）是家族性病例，但 ET 的遗传病因尚未得到很好的定义。连锁分析和全基因组关联研究（GWAS）已经确定了几个风险变体。近年来，ET 的外显子组测序揭示了 FUS（p.Q290X）、HTRA2（p.G399S）和 TENM4（c.4324 G>A、c.4100C>A 和 c.3412G>A）基因中的几个特定致病变体。
为了研究这三个基因对 ET 的遗传贡献，对来自中国东部的 238 名 ET 患者和 272 名对照者的 FUS、HTRA2 和 TENM4 的编码蛋白序列进行了直接 Sanger 测序分析。
我们在 FUS 中发现了两个同义编码单核苷酸多态性（SNP）rs741810 和 rs1052352，在 TENM4 中发现了三个先前报道的同义 SNP rs11237621、rs689369 和 rs2277277。在这些受试者中未发现非同义外显子变异。我们发现 rs1052352C 等位基因在 ET 组中的频率明显高于对照组（P =.001）。
总体而言，我们的研究结果表明 FUS 的 rs1052352 可能在中国人群中导致 ET 风险增加。
