A neurological disease caused by an expanded CAG trinucleotide repeat in the TATA-binding protein gene: a new polyglutamine disease?

To investigate whether the expansion of CAG repeats of the TATA-binding pro tein (TBP) gene is involved in the pathogenesis of neurodegenerative diseas es, we have screened 118 patients with various forms of neurological diseas e and identified a sporadic-onset patient with unique neurologic symptoms c onsisting of ataxia and intellectual deterioration associated with de novo expansion of the CAG repeat of the TBP gene, The mutant TBP with an expande d polyglutamine stretch (63 glutamines) was demonstrated to be expressed in lymphoblastoid cell lines at a level comparable with that of wild-type TBP , The CAG repeat of the TBP gene consists of impure CAG repeat and the de n ovo expansion involves partial duplication of the CAG repeat. The present s tudy provides new insights into sporadic-onset trinucleotide repeat disease s that involve de novo CAG repeat expansion.