Abstract
Fragile X-associated tremor/ataxia syndrome is a late adult onset neurodegenerative disorder that affects individuals who carry a premutation CGG repeat expansion (55-200 CGG repeats) in the 5′ untranslated portion of the fragile X mental retardation 1 (FMR1) gene. Affected individuals display cognitive decline, progressive intention tremor, gait ataxia, neuropathy, psychiatric symptoms, and parkinsonism; the severity of both clinical and neuropathological phenotypes is positively correlated with the extent of the CGG expansion. Overexpression of the expanded CGG repeat messenger RNA results in a direct gain-of-function cellular toxicity that is believed to form the pathogenic basis for fragile X-associated tremor/ataxia syndrome. This mechanism is entirely different from the mechanism giving rise to fragile X syndrome, which is due to transcriptional silencing and consequent loss of FMR1 protein. Much of the research in the field has focused on understanding the link between the pathogenic FMR1 messenger RNA and the potential proteins that interact with it.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 825-829 |
| Number of pages | 5 |
| Journal | Journal of Investigative Medicine |
| Volume | 57 |
| Issue number | 8 |
| DOIs | |
| State | Published - Dec 2009 |
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Keywords
- Autism
- CGG
- Fragile X
- Neurodegeneration
- Neuropathy
- Trinucleotide
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Molecular pathogenesis of fragile X-associated tremor/ataxia syndrome. / Raske, Christopher; Hagerman, Paul J.
In: Journal of Investigative Medicine, Vol. 57, No. 8, 12.2009, p. 825-829.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular pathogenesis of fragile X-associated tremor/ataxia syndrome
AU - Raske, Christopher
AU - Hagerman, Paul J
PY - 2009/12
Y1 - 2009/12
N2 - Fragile X-associated tremor/ataxia syndrome is a late adult onset neurodegenerative disorder that affects individuals who carry a premutation CGG repeat expansion (55-200 CGG repeats) in the 5′ untranslated portion of the fragile X mental retardation 1 (FMR1) gene. Affected individuals display cognitive decline, progressive intention tremor, gait ataxia, neuropathy, psychiatric symptoms, and parkinsonism; the severity of both clinical and neuropathological phenotypes is positively correlated with the extent of the CGG expansion. Overexpression of the expanded CGG repeat messenger RNA results in a direct gain-of-function cellular toxicity that is believed to form the pathogenic basis for fragile X-associated tremor/ataxia syndrome. This mechanism is entirely different from the mechanism giving rise to fragile X syndrome, which is due to transcriptional silencing and consequent loss of FMR1 protein. Much of the research in the field has focused on understanding the link between the pathogenic FMR1 messenger RNA and the potential proteins that interact with it.
AB - Fragile X-associated tremor/ataxia syndrome is a late adult onset neurodegenerative disorder that affects individuals who carry a premutation CGG repeat expansion (55-200 CGG repeats) in the 5′ untranslated portion of the fragile X mental retardation 1 (FMR1) gene. Affected individuals display cognitive decline, progressive intention tremor, gait ataxia, neuropathy, psychiatric symptoms, and parkinsonism; the severity of both clinical and neuropathological phenotypes is positively correlated with the extent of the CGG expansion. Overexpression of the expanded CGG repeat messenger RNA results in a direct gain-of-function cellular toxicity that is believed to form the pathogenic basis for fragile X-associated tremor/ataxia syndrome. This mechanism is entirely different from the mechanism giving rise to fragile X syndrome, which is due to transcriptional silencing and consequent loss of FMR1 protein. Much of the research in the field has focused on understanding the link between the pathogenic FMR1 messenger RNA and the potential proteins that interact with it.
KW - Autism
KW - CGG
KW - Fragile X
KW - Neurodegeneration
KW - Neuropathy
KW - Trinucleotide
UR - http://www.scopus.com/inward/record.url?scp=74249089729&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=74249089729&partnerID=8YFLogxK
U2 - 10.231/JIM.0b013e3181be329a
DO - 10.231/JIM.0b013e3181be329a
M3 - Article
C2 - 19794313
AN - SCOPUS:74249089729
VL - 57
SP - 825
EP - 829
JO - Journal of Investigative Medicine
JF - Journal of Investigative Medicine
SN - 1081-5589
IS - 8
ER -