Nakamura K, Jeong S Y, Uchihara T, Anno M, Nagashima K, Nagashima T, Ikeda S, Tsuji S, Kanazawa I
Department of Neurology, Division of Neuroscience, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Hum Mol Genet. 2001 Jul 1;10(14):1441-8. doi: 10.1093/hmg/10.14.1441.
Genetic etiologies of at least 20% of autosomal dominant cerebellar ataxias (ADCAs) have yet to be clarified. We identified a novel spinocerebellar ataxia (SCA) form in four Japanese pedigrees which is caused by an abnormal CAG expansion in the TATA-binding protein (TBP) gene, a general transcription initiation factor. Consequently, it has been added to the group of polyglutamine diseases. This abnormal expansion of glutamine tracts in TBP bears 47--55 repeats, whereas the normal repeat number ranges from 29 to 42. Immunocytochemical examination of a postmortem brain which carried 48 CAG repeats detected neuronal intranuclear inclusion bodies that stained with anti-ubiquitin antibody, anti-TBP antibody and with the 1C2 antibody that recognizes specifically expanded pathological polyglutamine tracts. We therefore propose that this new disease be called SCA17 (TBP disease).
至少20%的常染色体显性小脑共济失调（ADCA）的遗传病因尚未明确。我们在四个日本家系中鉴定出一种新型脊髓小脑共济失调（SCA），它是由通用转录起始因子TATA结合蛋白（TBP）基因中的CAG异常扩增引起的。因此，它已被归入多聚谷氨酰胺疾病组。TBP中谷氨酰胺序列的这种异常扩增有47 - 55个重复，而正常重复数范围为29至42。对一个携带48个CAG重复的死后大脑进行免疫细胞化学检查，发现神经元核内包涵体，这些包涵体用抗泛素抗体、抗TBP抗体以及识别特异性扩增的病理性多聚谷氨酰胺序列的1C2抗体染色。因此，我们提议将这种新疾病称为SCA17（TBP病）。
