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Molecular and Cellular Aspects of Mental Retardation in the Fragile X Syndrome: From Gene Mutation/s to Spine Dysmorphogenesis

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Synaptic Plasticity

Part of the book series: Advances in Experimental Medicine and Biology ((volume 970))

Abstract

The Fragile X syndrome (FXS) is the most frequent form of inherited mental retardation and also considered a monogenic cause of Autism Spectrum Disorder. FXS symptoms include neurodevelopmental delay, anxiety, hyperactivity, and autistic-like behavior. The disease is due to mutations or loss of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein abundant in the brain and gonads, the two organs mainly affected in FXS patients. FMRP has multiple functions in RNA metabolism, including mRNA decay, dendritic targeting of mRNAs, and protein synthesis. In neurons lacking FMRP, a wide array of mRNAs encoding proteins involved in synaptic structure and function are altered. As a result of this complex dysregulation, in the absence of FMRP, spine morphology and functioning is impaired. Consistently, model organisms for the study of the syndrome recapitulate the phenotype observed in FXS patients, such as dendritic spine anomalies and defects in learning.

Here, we review the fundamentals of genetic and clinical aspects of FXS, devoting a specific attention to ASD comorbidity and FXS-related diseases. We also review the current knowledge on FMRP functions through structural, molecular, and cellular findings. Finally, we discuss the neuroanatomical, electrophysiological, and behavioral defects caused by FMRP loss, as well as the current treatments able to partially revert some of the FXS abnormalities.

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Acknowledgments

This study was supported by Telethon, Compagnia di San Paolo, COFIN, FWO, and FP7 (SynSys). We are thankful to the Associazione Italiana Sindrome X Fragile (http://www.xfragile.net/).

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Authors and Affiliations

  1. Center for Human Genetics, Katholieke Universiteit Leuven, 3000, Leuven, Belgium

    Silvia De Rubeis, Esperanza Fernández, Andrea Buzzi, Daniele Di Marino & Claudia Bagni

  2. Center for the Biology of Disease, Flanders Institute for Biotechnology (VIB), 3000, Leuven, Belgium

    Silvia De Rubeis, Esperanza Fernández, Andrea Buzzi, Daniele Di Marino & Claudia Bagni

  3. Department of Experimental Medicine and Biochemical Sciences, University “Tor Vergata”, 00133, Rome, Italy

    Claudia Bagni

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  1. Silvia De Rubeis
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  2. Esperanza Fernández
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  3. Andrea Buzzi
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  4. Daniele Di Marino
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  5. Claudia Bagni
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Correspondence to Claudia Bagni .

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  1. , PG Neuroplasticity, Leibniz Institute for Neurobiology, Brenneckestraße 6, Magdeburg, 39118, Germany

    Michael R. Kreutz

  2. , Institute of Neuroscience, CR6 CNR-IN Consiglio Nazionale delle Ric, Via Vanvitelli, 32, Milano, 20129, Italy

    Carlo Sala

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De Rubeis, S., Fernández, E., Buzzi, A., Di Marino, D., Bagni, C. (2012). Molecular and Cellular Aspects of Mental Retardation in the Fragile X Syndrome: From Gene Mutation/s to Spine Dysmorphogenesis. In: Kreutz, M., Sala, C. (eds) Synaptic Plasticity. Advances in Experimental Medicine and Biology, vol 970. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0932-8_23

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