Disease onset in X-linked dystonia-parkinsonism correlates with expansion of a hexameric repeat within an SVA retrotransposon in TAF1

Significance The genetic basis of X-Linked dystonia-parkinsonism (XDP) has been difficult to unravel, in part because all patients inherit the same haplotype of seven sequence variants, none of which has ever been identified in control individuals. This study revealed that one of the haplotype markers, a retrotransposon insertion within an intron of TAF1 , has a variable number of hexameric repeats among affected individuals with an increase in repeat number strongly correlated with earlier age at disease onset. These data support a contributing role for this sequence in disease pathogenesis while further suggesting that XDP may be part of a growing list of neurodegenerative disorders associated with unstable repeat expansions.