Neuropathological, clinical and molecular pathology in female fragile X premutation carriers with and without FXTAS.

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Serval ID
serval:BIB_6EA57424A785
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Neuropathological, clinical and molecular pathology in female fragile X premutation carriers with and without FXTAS.
Journal
Genes, Brain, and Behavior
Author(s)
Tassone F., Greco C.M., Hunsaker M.R., Seritan A.L., Berman R.F., Gane L.W., Jacquemont S., Basuta K., Jin L.W., Hagerman P.J., Hagerman R.J.
ISSN
1601-183X (Electronic)
ISSN-L
1601-183X
Publication state
Published
Issued date
2012
Volume
11
Number
5
Pages
577-585
Language
english
Notes
Publication types: JOURNAL ARTICLEPublication Status: ppublish
Abstract
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.
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Create date
29/07/2012 14:16
Last modification date
20/08/2019 14:27
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