A nonpathogenic GAAGGA repeat in the Friedreich gene Implications for pathogenesis

An individual with late-onset ataxia was found to be heterozygous for an unusual (GAAGGA)65sequence and a normal GAA repeat in the frataxin gene. No frataxin point mutation was present, excluding a form of Friedreich ataxia. (GAAGGA)65did not have the inhibitory effect on gene expression in transfected cells shown by pathogenic GAA repeats of similar length. GAA repeats, but not (GAAGGA)65, adopt a triple helical conformation in vitro. We suggest that such a triplex structure is essential for suppression of gene expression.