Gene expression profiling in postmortem Rett syndrome brain: Differential gene expression and patient classification

The identification of mutations in the transcriptional repressor methyl-CpG -binding protein 2 (MECP2) gene in Rett Syndrome (RTT) suggests that an ina ppropriate release of transcriptional silencing may give rise to RTT neurop athology. Despite this progress, the molecular basis of RTT neuropathogenes is remains unclear. Using multiple cDNA microarray technologies, subtractiv e hybridization, and conventional biochemistry, we generated comprehensive gene expression profiles of postmortem brain tissue from RTT patients and m atched controls. Many glial transcripts involved in known neuropathological mechanisms were found to have increased expression in RTT brain, while dec reases were observed in the expression of multiple neuron-specific mRNAs. D ramatic and consistent decreases in transcripts encoding presynaptic marker s indicated a specific deficit in presynaptic development. Employing multip le clustering algorithms, it was possible to accurately segregate RTT from control brain tissue samples based solely on gene expression profile. Altho ugh previously achieved in cancers, our results constitute the first report of human disease classification using gene expression profiling in a compl ex tissue source such as brain. (C) 2001 Academic Press.