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Open Access Research article

Gene expression patterns vary in clonal cell cultures from Rett syndrome females with eight different MECP2 mutations

Jeff Traynor12, Priyanka Agarwal1, Laura Lazzeroni3 and Uta Francke124*

Author Affiliations

1 Department of Genetics, Stanford University School of Medicine, Stanford CA 94305, USA

2 Pediatrics, Stanford University School of Medicine, Stanford CA 94305, USA

3 Department of Health Research and Policy, Stanford University School of Medicine, Stanford CA 94305, USA

4 Address: Stanford University School of Medicine, Beckman Center for Molecular and Genetic Medicine, Room B201, 279 Campus Drive, Stanford, CA 94305-5323, USA

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BMC Medical Genetics 2002, 3:12  doi:10.1186/1471-2350-3-12

Published: 5 November 2002



Females with the neurological disorder Rett syndrome are heterozygous for mutations in X-linked MECP2 that encodes methyl-CpG binding protein 2 (MeCP2) thought to act as a transcriptional repressor. To identify target genes for MeCP2 modulation, we studied global gene expression in single cell-derived wild-type and mutant MECP2 expressing fibroblast clones with four common mutations (R106W, R306C, 705delG, 1155del32) and in lymphoblastoid cell lines (LCLs) that included four mutant MeCP2 (T158M, 803delG, R168X and 1159del28) expressing, and five (1159del28, R106W, R255X, 803delG, 803delG) wild-type MeCP2 expressing lines.


Clonality and mutation status were verified by androgen receptor methylation assays for X-inactivation and by sequencing MECP2 transcripts. Expression studies were done with oligonucleotide microarrays (Affymetrix U95) and verified with real-time quantitative RT-PCR using Sybr Green.


Expression of 49 transcripts was increased, and expression of 21 transcripts was decreased, in at least 3 of 4 mutant/wild-type fibroblast comparisons. Transcript levels of 11 genes, determined by quantitative RT-PCR, were highly correlated with the microarray data. Therefore, multiple additional clones from two Rett individuals were tested by RT-PCR only. Striking expression differences were found in both mutant and wildtype MeCP2 expressing clones. Comparing expression profiles of lymphoblastoid cell lines yielded 16 differentially expressed genes.


MeCP2 deficiency does not lead to global deregulation of gene expression. Either MeCP2's in vivo function does not involve widespread transcriptional repression, or its function is redundant in cell types that also express other methyl-CpG binding proteins. Our data suggest that clonal fibroblast strains may show substantial inter-strain variation, making them a difficult and unstable resource for genome-wide expression profiling studies.