Koide R, Kobayashi S, Shimohata T, Ikeuchi T, Maruyama M, Saito M, Yamada M, Takahashi H, Tsuji S
Department of Neurology, Niigata University, Japan.
Hum Mol Genet. 1999 Oct;8(11):2047-53. doi: 10.1093/hmg/8.11.2047.
To investigate whether the expansion of CAG repeats of the TATA-binding protein (TBP) gene is involved in the pathogenesis of neurodegenerative diseases, we have screened 118 patients with various forms of neurological disease and identified a sporadic-onset patient with unique neurologic symptoms consisting of ataxia and intellectual deterioration associated with de novo expansion of the CAG repeat of the TBP gene. The mutant TBP with an expanded polyglutamine stretch (63 glutamines) was demonstrated to be expressed in lymphoblastoid cell lines at a level comparable with that of wild-type TBP. The CAG repeat of the TBP gene consists of impure CAG repeat and the de novo expansion involves partial duplication of the CAG repeat. The present study provides new insights into sporadic-onset trinucleotide repeat diseases that involve de novo CAG repeat expansion.
为了研究TATA结合蛋白（TBP）基因的CAG重复序列扩增是否与神经退行性疾病的发病机制有关，我们对118例患有各种神经系统疾病的患者进行了筛查，并确定了一名散发型患者，其具有独特的神经系统症状，包括共济失调和智力衰退，与TBP基因CAG重复序列的从头扩增有关。具有扩展的聚谷氨酰胺序列（63个谷氨酰胺）的突变型TBP在淋巴母细胞系中的表达水平与野生型TBP相当。TBP基因的CAG重复序列由不纯的CAG重复序列组成，从头扩增涉及CAG重复序列的部分重复。本研究为涉及从头CAG重复序列扩增的散发型三核苷酸重复疾病提供了新的见解。
