Figure 6.

Evidence linking TAF1 to XDP pathogenesis. The region of Xq13.1 affected in the XDP allele is at the MTS, in which TAF1 lies. TAF1 from XDP patients or XDP carriers contains a novel SVA within intron 32, and cTAF1, nTAF1 and TAF1−32i show differential transcript levels in XDP brain compared with that without XDP. Changes to transcript levels may affect TAF1 protein levels in yet unknown ways (dotted arrow), including NMD of the transcript, preventing synthesis of TAF1 proteins. Other mechanisms of differential TAF1 expression may be owing to the length of the hexameric repeat in the SVA and the association of acetyl histone H3 with exon 32. Nonetheless, eventually the caudate nucleus and putamen regions of the neostriatum show atrophy, which is thought to be linked to the onset of dystonia and parkinsonism observed in XDP patients. Figure (introns and exons) not drawn to scale. Created with BioRender.com.