To study TAF1 expression in X-Linked Dystonia-Parkinsonism in patient derived neuro-precursor cells (NPCs) and secreted extracellular vesicles (EVs).

XDP is a rare neurological disease endemic to the Philippines with dystonia appearing at mean age of 39.7 years and progressing to parkinsonism with degenerative pathology in the striatum. A retrotransposon (SVA) inserted in intron 32 of the TAF1 gene leads to alternative splicing in the region and a reduction in the full length TAF1 transcript that has been shown in some patient derived cell lines but never in EVs or patient biofluids.

TAF1-32i splice variant expression was on average 28-fold higher in patient NPCs (n=10) compared to control NPCs (n=5) and on average 100-fold higher in patient NPC EVs compared to controls NPC EVs from the same cell lines. Normalized TAF1-3’ levels, but not TAF1-5’ levels, are significantly decreased by 27% in patient derived NPCs compared to controls. In EVs, TAF1-5’ was used as an internal control for TAF1-3’ expression. The corrected TAF1-3’ expression in EVs is 51% lower in patient samples compared to control samples.

Disease-specific TAF1 splice variant and TAF1 expression dysregulation can be detected and accurately quantified in patient derived NPCs and NPC EVs using different TAF1 primers. EVs could be isolated from patients’ blood or CSF to study TAF1 splice variant and TAF1 3’ expression.