CAG repeat expansion in the TATA box-binding protein gene causes autosomal dominant cerebellar ataxia.
1. Brain. 2001 Oct;124(Pt 10):1939-47.
CAG repeat expansion in the TATA box-binding protein gene causes autosomal
dominant cerebellar ataxia.
Fujigasaki H(1), Martin JJ, De Deyn PP, Camuzat A, Deffond D, Stevanin G, Dermaut
B, Van Broeckhoven C, Dürr A, Brice A.
(1)INSERM U289, Hôpital de la Salpêtrière, Paris, France.
At least 13 loci responsible for autosomal dominant cerebellar ataxia (ADCA) have
been identified. Spinocerebellar ataxia 1, 2, 3, 6 and 7 are caused by translated
CAG repeat expansions. However, in France, >30% of ADCAs are not explained by the
known genes. Recently, analysis of the TATA box-binding protein (TBP) gene, one
of the transcription factors known to contain a CAG/CAA repeat, in patients with
progressive cerebellar ataxia revealed one sporadic case with 63 repeats. We
examined this gene in 162 index cases with ADCA. An expanded repeat with 46
repeat units was detected in a single index case from Belgium. In this family,
two affected members and six unaffected, but at-risk, individuals carried
expanded alleles. Interestingly, the expanded repeat was stable during
transmission. The main clinical features in six patients were cerebellar ataxia,
dementia and behavioural disturbances with onset in their fourth to sixth decade.
The main neuropathological finding was severe neuronal loss and gliosis in the
Purkinje cell layer. Immunohistochemical analysis showed neuronal intranuclear
inclusions containing expanded polyglutamine, indicating that this disease shares
several features with other polyglutamine diseases. This study demonstrates that
CAG/CAA repeat expansion in the TBP gene causes ADCA with dementia and/or
PMID: 11571212 [Indexed for MEDLINE]