Different types of repeat expansion in the TATA-binding protein gene are associated with a new form of inherited ataxia

A novel neurological syndrome has recently been described to be associated with an expanded polyglutamine domain. The expansion results from partial d uplication within the TATA-binding protein (TBP). By investigation of 604 s poradic and familial cases with various forms of neurological syndromes and 157 unaffected individuals, we found repeat expansions in the TBP in four patients of two families with autosomal dominant inheritance of ataxia, dys tonia, and intellectual decline. Two different genotypes for the repetitive sequence could be demonstrated which led to elongated polyglutamine stretc hes between 50 and 55 residues, whereas normal alleles with 27 to a maximum of 44 glutamine residues were found in this study. The expansion to 50 or more glutamine residues results in a pathological phenotype and confirms th e report of a new polyglutamine disease.