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Target Concepts:
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Query: UMLS:C0234376 (
intention tremor
)
350
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Carriers of premutation within the FMR1 gene are typically normal intellectually, although a limited number of them have been reported to have either learning disabilities or mild dysmorphic features. A neurological condition involving
intention tremor
, ataxia and cognitive decline has recently been identified among older males carrying premutation alleles of the FMR1 gene, including grandfathers of children affected with fragile X syndrome. Characteristic findings from magnetic resonance imaging include cerebral and cerebellar volume loss and altered signal intensities of the middle cerebellar peduncles. This syndrome may represent one of the more common causes of tremor, ataxia and dementia among older males. The diagnosis of
FXTAS
is straightforward if a family at high genetic risk could be identified. Thus genetic counseling should be offered to such family.
...
PMID:[Fragile X-associated tremor/ataxia syndrome]. 1598 Nov 62
FXTAS
(Fragile X-associated tremor and ataxia syndrome) is a late- onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS), the most common cause of inherited mental retardation. Individuals affected by
FXTAS
generally present
intention tremor
and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization,
FXTAS
is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease.
...
PMID:The fragile x-associated tremor and ataxia syndrome (FXTAS). 2104 96
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by expanded CGG (CGG
exp
) trinucleotides in the 5'UTR of the
FMR1
gene encoding
fragile X mental retardation protein
(
FMRP
). The patients, with the number of the repeats ranging from 55 to 200, show specific manifestation of clinical symptoms that include
intention tremor
, gait ataxia, cognitive deficits, and brain atrophy. Accumulation of toxic polyglycine (FMRpolyG), a by-product of the CGG
exp
repeat-associated non-ATG (RAN) translation, is considered to be one of the main factors triggering neurodegenerative processes in FXTAS patients. Nevertheless, the nature of the FMRpolyG-induced cell damage, especially in the context of its soluble and inclusion-associated forms, is still elusive. Targeting either biosynthesis, cellular stability or aggregation capacity of toxic FMRpolyG could be considered as a potential therapeutic strategy for FXTAS. Therefore, we tested a variety of quantitative methods based on forced expression of genetic constructs carrying CGG
exp
repeats in the context of the
FMR1
5'UTR fused to
GFP, mCherry
or Firefly luciferase gene in or out of frame to the polyglycine encoding sequence. We show that FMRpolyG translation either from native or an AUG-induced start codon as well as the translation yield of the
FMRP
open reading frame equivalent located downstream of the CGG
exp
element can be effectively estimated using fluorescence microscopy, flow cytometry or luciferase assay. We also quantitatively estimated soluble fraction and insoluble form of FMRpolyG aggregated in foci using an electrophoretic separation of cell lysates and fluorescence microscopy, respectively. Importantly, we show that dependent on a fusion tag, FMRpolyG has a different potential for aggregate formation. Our established protocols enable sensitive tracking of
FMRP
and FMRpolyG quantitative and qualitative changes after treatment with potential therapeutic agents for FXTAS. Furthermore, they can be modified for application to other RAN translation- and aggregation-related diseases.
...
PMID:Quantitative Evaluation of Toxic Polyglycine Biosynthesis and Aggregation in Cell Models Expressing Expanded CGG Repeats. 2997 Oct 92
