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

Am J Hum Genet. 2007 Mar;80(3):393-406. doi: 10.1086/512129. Epub 2007 Jan 23.


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 (short interspersed nuclear element, variable number of tandem repeats, and Alu 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alu Elements / genetics
  • Blotting, Northern
  • Case-Control Studies
  • Chromosomes, Human, X / genetics*
  • DNA / genetics
  • Down-Regulation
  • Dystonia / genetics*
  • Dystonia / pathology
  • Female
  • Genes, X-Linked
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / pathology
  • Histone Acetyltransferases
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neurons / metabolism*
  • Neurons / pathology
  • Parkinsonian Disorders / genetics*
  • Parkinsonian Disorders / pathology
  • Pedigree
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repetitive Sequences, Nucleic Acid / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • TATA Box
  • TATA-Binding Protein Associated Factors / genetics*
  • Tandem Repeat Sequences / genetics
  • Transcription Factor TFIID / genetics*


  • RNA, Messenger
  • TATA-Binding Protein Associated Factors
  • Transcription Factor TFIID
  • DNA
  • Histone Acetyltransferases
  • TATA-binding protein associated factor 250 kDa

Associated data

  • GENBANK/AB191243