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Lessons from Fragile X Regarding Neurobiology, Autism, and Neurodegeneration

HAGERMAN, RANDI J. M.D.

Journal of Developmental & Behavioral Pediatrics: February 2006 - Volume 27 - Issue 1 - p 63-74
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ABSTRACT. The fragile X mental retardation 1 gene (FMR1) mutation causes two disorders: fragile X syndrome (FXS) in those with the full mutation and the fragile X-associated tremor/ataxia syndrome (FXTAS) in some older individuals with the premutation. FXS is caused by a deficiency of the FMR1 protein (FMRP) leading to dysregulation of many genes that create a phenotype with ADHD, anxiety, and autism. FXTAS is caused by the elevation of FMR1-mRNA to levels 2 to 8 times normal in the premutation. This causes an RNA gain of function toxicity leading to brain atrophy, white matter disease, neuronal and astrocytic inclusion formation, and subsequent ataxia, intention tremor, peripheral neuropathy, and cognitive decline. The neurobiology and pathophysiology of FXS and FXTAS are described in detail.

Department of Pediatrics, M.I.N.D. Institute, University of California Davis Health System, Sacramento, California

Address for reprints: Randi J. Hagerman, M.D., Department of Pediatrics, M.I.N.D. Institute, University of California Davis Health System, 2825 50th Street, Sacramento, CA 95817; e-mail: randi.hagerman@ucdmc.ucdavis.edu.

© 2006 Lippincott Williams & Wilkins, Inc.