Genomic and transcriptomic analyses distinguish classic Rett and Rett-like syndrome and reveals shared altered pathways

Department of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Genomics (Impact Factor: 2.28). 10/2010; 97(1):19-28. DOI: 10.1016/j.ygeno.2010.09.004
Source: PubMed


Rett syndrome (RTT) is an X-linked neurodevelopmental disorder characterized by derangements in nervous system especially in cognition and behavior. The present study aims to understand the molecular underpinnings of two subtypes of RTT, classic RTT and Rett-like, and to elucidate common pathways giving rise to common RTT phenotype using genomic and transcriptomic approaches. Mutation screening on selected nuclear genes revealed only MECP2 mutations in a subset of classic RTT patients. MLPA assays and mtDNA screenings were all negative. Genome-wide copy number analysis indicated a novel duplication on X chromosome. Transcriptional profiling revealed blood gene signatures that clearly distinguish classic RTT and RTT-like patients, as well as shared altered pathways in interleukin-4 and NF-κB signaling pathways in both subtypes of the syndrome. To our knowledge, this is the first report on investigating common regulatory mechanisms/signaling pathways that may be relevant to the pathobiology of the "common RTT" phenotype.

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    • "The more recent technology of cytogenomic microarray analysis (CMA) has identified an increasing number of copy number gains and losses present in patients with ASD [Cook and Scherer, 2008; Glessner et al., 2009; Colak et al., 2011] In 2009, Glessner et al. identified seven patients with ASD who had a chromosome 6 copy number loss involving the PARK2 gene region. Control patients did not show this copy number loss. "
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