Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism

X-linked dystonia- parkinsonism (XDP) is a movement disorder endemic to the Philippines. The disease locus, DYT3, has been mapped to Xq13.1. In a search for the causative gene, we performed genomic sequencing analysis, followed by expression analysis of XDP brain tissues. We found a disease- specific SVA ((s) under bar hort interspersed nuclear element, (v) under bar ariable number of tandem repeats, and (A) under bar lu composite) retrotransposon insertion in an intron of the TATA- binding protein-associated factor 1 gene (TAF1), which encodes the largest component of the TFIID complex, and significantly decreased expression levels of TAF1 and the dopamine receptor D2 gene (DRD2) in the caudate nucleus. We also identified an abnormal pattern of DNA methylation in the retrotransposon in the genome from the patient's caudate, which could account for decreased expression of TAF1. Our findings suggest that the reduced neuron-specific expression of the TAF1 gene is associated with XDP.