SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein.
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).
Nakamura
K
K
Department of Neurology, Division of Neuroscience, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. koichiro-tky@umin.ac.jp
Jeong
S Y
SY
Uchihara
T
T
Anno
M
M
Nagashima
K
K
Nagashima
T
T
Ikeda
S
S
Tsuji
S
S
Kanazawa
I
I
D000328:Adult; D001921:Brain / Q000473:pathology; D002524:Cerebellar Ataxia / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009474:Neurons / Q000473:pathology; D010375:Pedigree; D010455:Peptides / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics
D004268:DNA-Binding Proteins; D010455:Peptides; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; C097188:polyglutamine