Document Detail


Fragile X-associated tremor/ataxia syndrome (FXTAS).
MedLine Citation:
PMID:  14994285     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Carriers of fragile X mental retardation 1 (FMR1) premutation alleles (55 to 200 CGG repeats) are generally spared the more serious neurodevelopmental problems associated with the full-mutation carriers (>200 repeats) of fragile X syndrome. However, some adult male premutation carriers (55-200 repeats) develop a neurological syndrome involving intention tremor, ataxia, dementia, parkinsonism, and autonomic dysfunction. In excess of one-third of male premutation carriers over 50 years of age develop the fragile X-associated tremor/ataxia syndrome (FXTAS). FXTAS also represents a new form of inclusion disease, with eosinophilic intranuclear inclusions found throughout the brain in both neurons and astrocytes. Because FXTAS appears to be relatively specific to male premutation carriers, who are known to possess elevated levels of FMR1 mRNA, the neuropathology may arise as a consequence of a toxic gain-of-function of the mRNA itself, although this proposal requires additional direct testing. One of the critical needs at present is a better estimate for the prevalence of this disorder, because FXTAS is likely to be underdiagnosed in the adult movement disorders clinics.
Authors:
Paul J Hagerman; Randi J Hagerman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Mental retardation and developmental disabilities research reviews     Volume:  10     ISSN:  1080-4013     ISO Abbreviation:  Ment Retard Dev Disabil Res Rev     Publication Date:  2004  
Date Detail:
Created Date:  2004-03-02     Completed Date:  2004-07-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9517974     Medline TA:  Ment Retard Dev Disabil Res Rev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  25-30     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Wiley-Liss, Inc.
Affiliation:
Department of Biological Chemistry, University of California, Davis, School of Medicine, Davis, California 95616, USA. pjhagerman@ucdavis.edu
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MeSH Terms
Descriptor/Qualifier:
Aging
Ataxia / genetics*,  pathology
Female
Fragile X Mental Retardation Protein
Fragile X Syndrome / genetics*
Heterozygote*
Humans
Magnetic Resonance Imaging
Male
Nerve Tissue Proteins / genetics
RNA, Messenger / analysis
RNA-Binding Proteins*
Syndrome
Tremor / genetics*,  pathology
Trinucleotide Repeats
Grant Support
ID/Acronym/Agency:
HD36071/HD/NICHD NIH HHS; HD40661/HD/NICHD NIH HHS; NS43532/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/FMR1 protein, human; 0/Nerve Tissue Proteins; 0/RNA, Messenger; 0/RNA-Binding Proteins; 139135-51-6/Fragile X Mental Retardation Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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