| Summary: | <p>Abstract</p> <p>Background</p> <p>More than 85% of Rett syndrome (RTT) patients have heterozygous mutations in the X-linked <it>MECP2 </it>gene which encodes methyl-CpG-binding protein 2, a transcriptional repressor that binds methylated CpG sites. Because <it>MECP2 </it>is subject to X chromosome inactivation (XCI), girls with RTT express either the wild type or mutant <it>MECP2 </it>in each of their cells. To test the hypothesis that <it>MECP2 </it>mutations result in genome-wide transcriptional deregulation and identify its target genes in a system that circumvents the functional mosaicism resulting from XCI, we performed gene expression profiling of pure populations of untransformed T-lymphocytes that express either a mutant or a wild-type allele.</p> <p>Methods</p> <p>Single T lymphocytes from a patient with a c.473C>T (p.T158M) mutation and one with a c.1308-1309delTC mutation were subcloned and subjected to short term culture. Gene expression profiles of wild-type and mutant clones were compared by oligonucleotide expression microarray analysis.</p> <p>Results</p> <p>Expression profiling yielded 44 upregulated genes and 77 downregulated genes. We compared this gene list with expression profiles of independent microarray experiments in cells and tissues of RTT patients and mouse models with <it>Mecp2 </it>mutations. These comparisons identified a candidate MeCP2 target gene, <it>SPOCK1</it>, downregulated in two independent microarray experiments, but its expression was not altered by quantitative RT-PCR analysis on brain tissues from a RTT mouse model.</p> <p>Conclusion</p> <p>Initial expression profiling from T-cell clones of RTT patients identified a list of potential MeCP2 target genes. Further detailed analysis and comparison to independent microarray experiments did not confirm significantly altered expression of most candidate genes. These results are consistent with other reported data.</p>
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