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- Vol.41 No.12
- CLINICA NEUROL, 41: 1123－1125, 2001
- Vol.41 No.12 contents
The 42nd Annual Meeting of the Japanese Society of Neurology
Symposium VI-4: Hereditary ataxic disorders
SCA17, a novel polyglutamine disease caused by the expansion of polyglutamine tracts in TATA-binding protein
Koichiro Nakamura, M. D.
Department of Neurology, Tokyo University School of Medicine
We have recently identified a novel SCA form in nine patients from four Japanese pedigrees through the screening for expanded polyglutamine tracts by Western blotting analysis with a monoclonal 1 C 2 antibody that recognizes specifically pathological polyglutamine tracts. This disease is caused by an abnormal CAG/CAA expansion in the TATA-binding protein gene (TBP), a general transcription initiation factor. This abnormal expansion of glutamine tracts in TBP ranges 47 to 55 repeats, whereas the normal repeat nuber ranges from 29 to 42. Immunocytochemical examination of a postmortem brain that carried 48 CAG repeats detected neuronal intranuclear inclusion bodies (NIIs) that stained with anti-ubiquitin antibody, anti-TBP antibody and with the1C2antibody. Most patients presented in the third decade with gait ataxia and dementia, progressing over several decades to include bradykinesia, dysmetria, dysdiadockokinesis, hyperreflexia and paucity of movement. No abnormal eye movements were present in any patient. This disease resembles the spinocerebellar ataxias including Dentato-rubal pallidoluysian atrophy (DRPLA) more closely than any other form of neurodegenerative disorder. Further study of this disease should provide important information for unraveling the molecular pathogenesis of neuronal cell degeneration as well as for the development of future therpeutic interventions.
(CLINICA NEUROL, 41: 1123－1125, 2001)
key words: polyglutamine disease, CAG repeat, TBP, parkinsonism, dementia
(Received: 13-May-01)
