The story of Rett syndrome: from clinic to neurobiology.

By Maria H. Chahrour, H. Zoghbi. Neuron, 2007

1,290 citations recorded by the source corpus.

The postnatal neurodevelopmental disorder Rett syndrome (RTT) is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2), a transcriptional repressor involved in chromatin remodeling and the modulation of RNA splicing. MECP2 aberrations result in a constellation of neuropsychiatric abnormalities, whereby both loss of function and gain in MECP2 dosage lead to similar neurological phenotypes. Recent studies demonstrate disease reversibility in RTT mouse models, suggesting that the neurological defects in MECP2 disorders are not permanent. To investigate the potential for restoring neuronal function in RTT patients, it is essential to identify MeCP2 targets or modifiers of the phenotype that can be therapeutically modulated. Moreover, deciphering the molecular underpinnings of RTT is likely to contribute to the understanding of the pathogenesis of a broader class of neuropsychiatric disorders.

Subfields: Cognitive Neuroscience, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d78b7a813f8b4d57f09333c231b7717049971910

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In Cognitive Neuroscience

1. M. O’Connell
2. O. Marín
3. O. Almeida
4. K. Warner
5. T. Boat

In Genetics

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2. Chuan He
3. Peng Jin
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In Molecular Biology

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5. O. Marín
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8. Xuekun Li

Citations in the corpus

• 5-hmC–mediated epigenetic dynamics during postnatal neurodevelopment and aging (2011, background): “Mutations in genes encoding proteins that directly bind to methylated DNA (methyl-CpG–binding proteins such as methyl-CpG–binding protein 2, MeCP2) or place 5-mC marks (DNA methyltransferase, DNMT3B) result in distinct neurodevelopmental disorders involving dysregulation of both coding genes and rep”
• Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities (2009, background): “models (Chang, Bray, et al., 2008; Bear, Dolen, et al., 2008; Chahrour and Zoghbi, 2007; Dolen, Osterweil, et al., 2007; Giacometti, Luikenhuis, et al., 2007; Guy, Gan, et al., 2007).”
• Somatic retrotransposition alters the genetic landscape of the human brain (2011, background): “For example, deletion of the chromatin remodeling HDAC1 cofactor MeCP2 12,25 leads to increased L1 copy number and may inhibit neuronal maturation in Rett syndrome 30 .”
• Dynamic DNA methylation programs persistent adverse effects of early-life stress (2009, background): “In this respect, certain parallels may be drawn between the mechanisms underlying ELS and Rett syndrome; the latter, caused by mutations in Mecp2 , also presents with altered cognitive, mood and HPA axis functio”
• Therapeutic application of histone deacetylase inhibitors for central nervous system disorders (2008, background): “MECP2 is a transcriptional repressor involved in chromatin remodelling and modulation of RNA splicin”
• Interneuron dysfunction in psychiatric disorders (2012, background): “Such a scenario probably occurs in Rett's syndrome, an autism spectrum disorder (ASD) that is characterized by impaired language skills, cognitive deficits, stereotypic behaviours and respiratory problem”