Abstract
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late adult onset neurodegenerative disorder that mainly affects male carriers of an allele of 55-200 CGG repeats in the FMR1 gene (premutation). FXTAS symptoms include progressive intention tremor, gait ataxia, neuropathy, psychiatric symptoms, cognitive decline, and autonomic dysfunctions. Neuropathological features of FXTAS include global cerebral and cerebellar atrophy, spongiform changes of white matter, marked Purkinje cell dropout and presence of ubiquitin-positive intranuclear inclusions throughout the brain. In contrast to fragile X Syndrome (FXS), FXTAS is associated with elevated expression of repeat containing FMR1 mRNA, which binds to and sequesters specific RNA binding proteins and impedes their normal functions. In addition, the CGG repeat expansion triggers a non-canonical translational initiation event to produce a polyglycine containing protein (FMRpolyG) that accumulates in patients brains. Here we discuss these and other putative molecular mechanisms for FXTAS pathogenesis with a focus on recent findings.
| Original language | English (US) |
|---|---|
| Title of host publication | FXTAS, FXPOI, and Other Premutation Disorders |
| Publisher | Springer International Publishing |
| Pages | 101-127 |
| Number of pages | 27 |
| ISBN (Electronic) | 9783319338989 |
| ISBN (Print) | 9783319338965 |
| DOIs | |
| State | Published - Jan 1 2016 |
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Keywords
- Antisense
- Disease mechanisms
- Neurodegenerative disease
- RAN translation
- RNA disease
- Transcription
ASJC Scopus subject areas
- Medicine(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Neuroscience(all)
Cite this
The molecular biology of premutation expanded alleles. / Tassone, Flora; Sellier, Chantal; Charlet-Berguerand, Nicolas; Todd, Peter K.
FXTAS, FXPOI, and Other Premutation Disorders. Springer International Publishing, 2016. p. 101-127.Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - The molecular biology of premutation expanded alleles
AU - Tassone, Flora
AU - Sellier, Chantal
AU - Charlet-Berguerand, Nicolas
AU - Todd, Peter K.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late adult onset neurodegenerative disorder that mainly affects male carriers of an allele of 55-200 CGG repeats in the FMR1 gene (premutation). FXTAS symptoms include progressive intention tremor, gait ataxia, neuropathy, psychiatric symptoms, cognitive decline, and autonomic dysfunctions. Neuropathological features of FXTAS include global cerebral and cerebellar atrophy, spongiform changes of white matter, marked Purkinje cell dropout and presence of ubiquitin-positive intranuclear inclusions throughout the brain. In contrast to fragile X Syndrome (FXS), FXTAS is associated with elevated expression of repeat containing FMR1 mRNA, which binds to and sequesters specific RNA binding proteins and impedes their normal functions. In addition, the CGG repeat expansion triggers a non-canonical translational initiation event to produce a polyglycine containing protein (FMRpolyG) that accumulates in patients brains. Here we discuss these and other putative molecular mechanisms for FXTAS pathogenesis with a focus on recent findings.
AB - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late adult onset neurodegenerative disorder that mainly affects male carriers of an allele of 55-200 CGG repeats in the FMR1 gene (premutation). FXTAS symptoms include progressive intention tremor, gait ataxia, neuropathy, psychiatric symptoms, cognitive decline, and autonomic dysfunctions. Neuropathological features of FXTAS include global cerebral and cerebellar atrophy, spongiform changes of white matter, marked Purkinje cell dropout and presence of ubiquitin-positive intranuclear inclusions throughout the brain. In contrast to fragile X Syndrome (FXS), FXTAS is associated with elevated expression of repeat containing FMR1 mRNA, which binds to and sequesters specific RNA binding proteins and impedes their normal functions. In addition, the CGG repeat expansion triggers a non-canonical translational initiation event to produce a polyglycine containing protein (FMRpolyG) that accumulates in patients brains. Here we discuss these and other putative molecular mechanisms for FXTAS pathogenesis with a focus on recent findings.
KW - Antisense
KW - Disease mechanisms
KW - Neurodegenerative disease
KW - RAN translation
KW - RNA disease
KW - Transcription
UR - http://www.scopus.com/inward/record.url?scp=85018901530&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018901530&partnerID=8YFLogxK
U2 - 10.1007/978-3-319-33898-9_6
DO - 10.1007/978-3-319-33898-9_6
M3 - Chapter
AN - SCOPUS:85018901530
SN - 9783319338965
SP - 101
EP - 127
BT - FXTAS, FXPOI, and Other Premutation Disorders
PB - Springer International Publishing
ER -