Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1(0 1):S147-9. doi: 10.1016/S1353-8020(13)70035-X.
Mutations of the FUS gene were first reported to cause amyotrophic lateral sclerosis (ALS). Subsequent studies confirmed the role of mutations in ALS and also implicated them in frontotemporal dementia (FTD). Recently, through Next-Generation Exome sequencing approaches a mutation resulting in a substitution (p.Q290X) in the nuclear export domain of the FUS protein was nominated as a cause of autosomal dominant essential tremor (ET) in a large kindred. In addition, recent reports suggest a possible role for TDP-43 mutations in parkinsonism; TDP-43 is another RNA-binding protein implicated in ALS. Given these findings we investigated the role of FUS variants in Parkinson's disease (PD). We sequenced specific regions of the gene encoding three functional domains of the FUS protein in 702 patients with PD. Our sequencing study did not identify any novel non-synonymous variant that would appear to affect the subjects' susceptibility to Parkinson's disease. These findings and previous studies have shown that variants within the FUS gene are not a common cause of PD or ET, in comparison to their role in ALS.
FUS 基因突变首先被报道导致肌萎缩侧索硬化症（ALS）。随后的研究证实了突变在 ALS 中的作用，并暗示它们也与额颞叶痴呆（FTD）有关。最近，通过下一代外显子测序方法，在一个大家族中发现 FUS 蛋白核输出结构域的一个突变（p.Q290X）导致常染色体显性特发性震颤（ET）。此外，最近的报道表明 TDP-43 突变可能在帕金森病中起作用；TDP-43 是另一种与 ALS 相关的 RNA 结合蛋白。鉴于这些发现，我们研究了 FUS 变体在帕金森病（PD）中的作用。我们对 702 名 PD 患者的 FUS 蛋白三个功能域的基因进行了特定区域的测序。我们的测序研究没有发现任何新的非同义变异，这些变异似乎会影响患者患帕金森病的易感性。这些发现和以前的研究表明，与 ALS 相比，FUS 基因内的变异不是 PD 或 ET 的常见原因。
