Department of Neurology, Chang Gung Memorial Hospital and Chang-Gung University College of Medicine, Taipei, Taiwan.
Clin Chim Acta. 2010 Mar;411(5-6):375-80. doi: 10.1016/j.cca.2009.12.002. Epub 2009 Dec 11.
Spinocerebellar ataxia type 17 (SCA17) involves the expression of a CAG/CAA expansion mutation in the gene encoding TATA-box binding protein (TBP), a general transcription initiation factor. The spectrum of SCA17 clinical presentation is broad.
We screened for triplet expansion in the TBP gene in Taiwanese Parkinson's disease (PD), Alzheimer's disease (AD) and atypical parkinsonism and investigated the functional implication of expanded alleles using lymphoblastoid cells as a model.
A total of 6 mildly expanded alleles (44-46) were identified in patients group. The frequency of the individuals carrying expanded alleles in PD (3/602 [0.5%]), AD (2/245 [0.8%]) and atypical parkinsonism (1/44 [2.3%]) is not significant as compared to that in the control subjects (0/644 [0.0%]). In lymphoblastoid cells, HSPA5, HSPA8 and HSPB1 expression levels in cells with expanded TBP were significantly lower than that of the control cells. Although not significantly, the levels of PARK7 protein isoforms 6.1 and 6.4 are notably increased in SCA17 lymphoblastoid cells. Treatment of TBH (tert-butyl hydroperoxide) significantly increases cell death in the cells with mildly expanded TBP.
Our findings expand the spectrum of SCA17 phenotype and may contribute to our understanding of the disease.
脊髓小脑共济失调 17 型（SCA17）涉及编码 TATA 框结合蛋白（TBP）的基因中 CAG/CAA 扩展突变的表达，TBP 是一种通用转录起始因子。SCA17 的临床表现谱很广。
我们在台湾的帕金森病（PD）、阿尔茨海默病（AD）和非典型帕金森病患者中筛选 TBP 基因中的三核苷酸扩展，并使用淋巴母细胞作为模型研究扩展等位基因的功能意义。
在患者组中发现了总共 6 个轻度扩展的等位基因（44-46）。携带扩展等位基因的个体在 PD（3/602[0.5%]）、AD（2/245[0.8%]）和非典型帕金森病（1/44[2.3%]）中的频率与对照组（0/644[0.0%]）相比没有显著差异。在淋巴母细胞中，携带扩展 TBP 的细胞中 HSPA5、HSPA8 和 HSPB1 的表达水平明显低于对照细胞。尽管不显著，但 SCA17 淋巴母细胞中 PARK7 蛋白同工型 6.1 和 6.4 的水平明显增加。TBH（叔丁基过氧化氢）处理显著增加了轻度扩展 TBP 细胞的细胞死亡。
我们的发现扩展了 SCA17 表型谱，并可能有助于我们了解该疾病。
