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Science 31 October 2003:
Vol. 302. no. 5646, pp. 826 - 830
DOI: 10.1126/science.1089071
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Postnatal Neurodevelopmental Disorders: Meeting at the Synapse?

Huda Y. Zoghbi

We often think of neurodevelopmental disorders as beginning before birth, and many certainly do. A handful, however, strike many months after birth, following a period of apparently normal growth and development. Autism and Rett syndrome are two such disorders, and here I consider some of their similarities at the phenotypic and pathogenic levels. I propose that both disorders result from disruption of postnatal or experience-dependent synaptic plasticity.

Departments of Pediatrics, Neurology, and Molecular and Human Genetics, Division of Neuroscience, and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.

E-mail: hzoghbi{at}bcm.tmc.edu

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   Abstract »    Full Text »    PDF »
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   Abstract »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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J. Zhang, A. Moseley, A. G. Jegga, A. Gupta, D. P. Witte, M. Sartor, M. Medvedovic, S. S. Williams, C. Ley-Ebert, L. M. Coolen, et al. (2004)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »


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