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Patho-Epigenetics of Disease pp 43–69Cite as

Dysfunction of the Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome

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Abstract

Rett syndrome (RTT) is a neurodevelopmental disorder predominantly occurring in females with an incidence of 1:10,000 births and caused by sporadic mutations in the MECP2 gene, which encodes methyl-CpG-binding protein-2, an epigenetic transcription factor that binds methylated DNA. The clinical hallmarks include a period of apparently normal early development followed by a plateau and then subsequent frank regression. Impaired visual and aural contact often leads to an initial diagnosis of autism. The characterization of experimental models based on the loss-of-function of the mouse Mecp2 gene revealed that subtle changes in the morphology and function of brain cells and synapses have profound consequences on network activities that underlie critical brain functions. Furthermore, these experimental models have been used for successful reversals of RTT-like symptoms by genetic, pharmacological, and environmental manipulations, raising hope for novel therapeutic strategies to improve the quality of life of RTT individuals.

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Acknowledgements

We thank Dr. Carolyn Schanen for useful comments on the manuscript. This is supported by NIH grants from NINDS (NS40593, NS057780, NS-065027) and NICHD (U54 grant HD061222 and IDDRC grant HD38985), IRSF, and the Civitan Foundation. The authors acknowledge the gracious participation and provision of information by families in the Rare Disease Natural History Study for which Dr. Mary Lou Oster-Granite, Health Scientist Administrator at NICHD, provided invaluable guidance, support, and encouragement.

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  1. Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, AL, USA

    Gaston Calfa & Lucas Pozzo-Miller

  2. Departments of Pediatrics, Neurology, and Genetics, Civitan International Research Center, Birmingham, AL, USA

    Alan K. Percy

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  1. Gaston Calfa
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Correspondence to Lucas Pozzo-Miller .

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  1. Microbiological Research Group, National Center for Epidemiology, Piheno u. 1, Budapest, 1529, Hungary

    Janos Minarovits

  2. University of Regensburg, Regensburg, 93053, Germany

    Hans Helmut Niller

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Calfa, G., Percy, A.K., Pozzo-Miller, L. (2012). Dysfunction of the Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome. In: Minarovits, J., Niller, H. (eds) Patho-Epigenetics of Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3345-3_3

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