脊髓小脑共济失调17型（SCA17），一种由TATA结合蛋白中多聚谷氨酰胺扩增引起的新型常染色体显性遗传性小脑共济失调。

SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein.

作者信息

Nakamura K, Jeong S Y, Uchihara T, Anno M, Nagashima K, Nagashima T, Ikeda S, Tsuji S, Kanazawa I

机构信息

Department of Neurology, Division of Neuroscience, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

出版信息

Hum Mol Genet. 2001 Jul 1;10(14):1441-8. doi: 10.1093/hmg/10.14.1441.

DOI:10.1093/hmg/10.14.1441

PMID:11448935

Abstract

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).

摘要

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）。