Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Parkinsonism Relat Disord. 2013 Aug;19(8):755-7. doi: 10.1016/j.parkreldis.2013.03.005. Epub 2013 Apr 16.
Essential Tremor is the most common form of movement disorder. Aggregation in families suggests a strong genetic component to disease. Linkage and association studies have identified several risk loci but the specific causal variants are still unknown. A recent study using whole exome sequencing identified a rare nonsense variant in the FUS gene (p.Q290X) that segregated with Essential Tremor in a large French Canadian family. In addition, two other rare FUS variants were identified (p.R216C and p.P431L) in Essential Tremor patients however co-segregation analysis with disease was not possible. In the present study, we sequenced all 15 exons of FUS in 152 familial probands with Essential Tremor and genotyped three reported FUS variants in 112 sporadic Essential Tremor patients and 716 control subjects recruited at Mayo Clinic Florida. Only known synonymous SNPs unlikely to be pathogenic were detected in our sequencing and not any of the recently identified mutations or novel ones. We conclude that the FUS mutations associated with risk of Essential Tremor are probably a rare occurrence.
特发性震颤是最常见的运动障碍。家族聚集表明该病具有很强的遗传成分。连锁和关联研究已经确定了几个风险位点，但具体的致病变异仍然未知。最近的一项全外显子组测序研究发现，在一个大型法裔加拿大家族中，FUS 基因（p.Q290X）的一个罕见无义变异与特发性震颤共分离。此外，还在特发性震颤患者中发现了另外两种罕见的 FUS 变异（p.R216C 和 p.P431L），但与疾病的共分离分析是不可能的。在本研究中，我们对 152 名有家族史的特发性震颤先证者的 FUS 的 15 个外显子进行了测序，并对 112 名散发性特发性震颤患者和在佛罗里达州梅奥诊所招募的 716 名对照进行了三种已报道的 FUS 变异的基因分型。在我们的测序中仅发现了一些不太可能致病的已知同义 SNP，而没有发现最近发现的突变或新的突变。我们的结论是，与特发性震颤风险相关的 FUS 突变可能是罕见事件。
