Document Detail


Neuropathological, clinical and molecular pathology in female fragile X premutation carriers with and without FXTAS.
MedLine Citation:
PMID:  22463693     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder associated with premutation alleles of the fragile X mental retardation 1 (FMR1) gene. Approximately 40% of older male premutation carriers, and a smaller proportion of females, are affected by FXTAS; due to the lower penetrance the characterization of the disorder in females is much less detailed. Core clinical features of FXTAS include intention tremor, cerebellar gait ataxia and frequently parkinsonism, autonomic dysfunction and cognitive deficits progressing to dementia in up to 50% of males. In this study, we report the clinical, molecular and neuropathological findings of eight female premutation carriers. Significantly, four of these women had dementia; of the four, three had FXTAS plus dementia. Post-mortem examination showed the presence of intranuclear inclusions in all eight cases, which included one asymptomatic premutation carrier who died from cancer. Among the four subjects with dementia, three had sufficient number of cortical amyloid plaques and neurofibrillary tangles to make Alzheimer's disease a highly likely cause of dementia and a fourth case had dementia with cortical Lewy bodies. Dementia appears to be more common than originally reported in females with FXTAS. Although further studies are required, our observation suggests that in a portion of FXTAS cases there is Alzheimer pathology and perhaps a synergistic effect on the progression of the disease may occur.
Authors:
F Tassone; C M Greco; M R Hunsaker; A L Seritan; R F Berman; L W Gane; S Jacquemont; K Basuta; L-W Jin; P J Hagerman; R J Hagerman
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-06
Journal Detail:
Title:  Genes, brain, and behavior     Volume:  11     ISSN:  1601-183X     ISO Abbreviation:  Genes Brain Behav.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-11-20     Revised Date:  2014-03-31    
Medline Journal Info:
Nlm Unique ID:  101129617     Medline TA:  Genes Brain Behav     Country:  England    
Other Details:
Languages:  eng     Pagination:  577-85     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Alleles
Ataxia / genetics*,  pathology
Brain / pathology*
Dementia / genetics*,  pathology
Female
Fragile X Mental Retardation Protein / genetics*
Fragile X Syndrome / genetics*,  pathology
Humans
Intranuclear Inclusion Bodies / genetics,  pathology
Middle Aged
Neurons / pathology
Syndrome
Tremor / genetics*,  pathology
Grant Support
ID/Acronym/Agency:
AG032115/AG/NIA NIH HHS; HD036071/HD/NICHD NIH HHS; P30 HD002274/HD/NICHD NIH HHS; UL1DE019583/DE/NIDCR NIH HHS; UL1RR024116/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/FMR1 protein, human; 139135-51-6/Fragile X Mental Retardation Protein
Comments/Corrections

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