Gene expression profiling in postmortem Rett Syndrome brain: differential gene expression and patient classification

Neurobiol Dis. 2001 Oct;8(5):847-65. doi: 10.1006/nbdi.2001.0428.


The identification of mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MECP2) gene in Rett Syndrome (RTT) suggests that an inappropriate release of transcriptional silencing may give rise to RTT neuropathology. Despite this progress, the molecular basis of RTT neuropathogenesis remains unclear. Using multiple cDNA microarray technologies, subtractive hybridization, and conventional biochemistry, we generated comprehensive gene expression profiles of postmortem brain tissue from RTT patients and matched controls. Many glial transcripts involved in known neuropathological mechanisms were found to have increased expression in RTT brain, while decreases were observed in the expression of multiple neuron-specific mRNAs. Dramatic and consistent decreases in transcripts encoding presynaptic markers indicated a specific deficit in presynaptic development. Employing multiple clustering algorithms, it was possible to accurately segregate RTT from control brain tissue samples based solely on gene expression profile. Although previously achieved in cancers, our results constitute the first report of human disease classification using gene expression profiling in a complex tissue source such as brain.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Algorithms
  • Amino Acid Sequence
  • Blotting, Southern
  • Brain / enzymology*
  • Cause of Death
  • Child
  • Child, Preschool
  • Chromosomal Proteins, Non-Histone*
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Dosage Compensation, Genetic
  • Female
  • Gene Expression Profiling*
  • Humans
  • Methyl-CpG-Binding Protein 2
  • Molecular Sequence Data
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Neuroglia / metabolism
  • Neurons / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Postmortem Changes*
  • RNA, Messenger / biosynthesis
  • Repressor Proteins*
  • Rett Syndrome / genetics*
  • Rett Syndrome / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Subtraction Technique


  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Repressor Proteins

Associated data

  • OMIM/312750