Fragile X-associated tremor/ataxia syndrome: Intrafamilial variability and the size of theFMR1 premutation CGG repeat

2007 ◽  
Vol 22 (6) ◽  
pp. 866-870 ◽  
Author(s):  
Leonardo P. Capelli ◽  
Márcia R. R. Gonçalves ◽  
Fernando Kok ◽  
Cláudia C. Leite ◽  
Ricardo Nitrini ◽  
...  
Keyword(s):  
Fragile X ◽  
Cgg Repeat ◽  
Intrafamilial Variability ◽  
Ataxia Syndrome

CGG repeat length correlates with age of onset of motor signs of the fragile X-associated tremor/ataxia syndrome (FXTAS)

2007 ◽  
Vol 144B (4) ◽  
pp. 566-569 ◽  
Author(s):  
Flora Tassone ◽  
John Adams ◽  
Elizabeth M. Berry-Kravis ◽  
Susannah S. Cohen ◽  
Alfredo Brusco ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Fragile X ◽  
Repeat Length ◽  
Cgg Repeat ◽  
Ataxia Syndrome

scholarly journals ASFMR1splice variant

2018 ◽  
Vol 4 (4) ◽  
pp. e246 ◽  
Author(s):  
Padmaja Vittal ◽  
Shrikant Pandya ◽  
Kevin Sharp ◽  
Elizabeth Berry-Kravis ◽  
Lili Zhou ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Splice Variant ◽  
Messenger Rna ◽  
Clinical Symptoms ◽  
Fragile X ◽  
Cgg Repeat ◽  
Men And Women ◽  
Fragile X Mental Retardation ◽  
Repeat Size ◽  
Ataxia Syndrome

ObjectiveTo explore the association of a splice variant of theantisense fragile X mental retardation 1(ASFMR1) gene, loss offragile X mental retardation 1(FMR1) AGG interspersions andFMR1CGG repeat size with manifestation, and severity of clinical symptoms of fragile X-associated tremor/ataxia syndrome (FXTAS).MethodsPremutation carriers (PMCs) with FXTAS, without FXTAS, and normal controls (NCs) had a neurologic evaluation and collection of skin and blood samples. Expression ofASFMR1transcript/splice variant 2 (ASFMR1-TV2), nonsplicedASFMR1, totalASFMR1, andFMR1messenger RNA were quantified and compared using analysis of variance. Least absolute shrinkage and selection operator (LASSO) logistic regression and receiver operating characteristic analyses were performed.ResultsPremutation men and women both with and without FXTAS had higherASFMR1-TV2 levels compared with NC men and women (n = 135,135,p< 0.0001), andASFMR1-TV2 had good discriminating power for FXTAS compared with NCs but not for FXTAS from PMC. After adjusting for age, loss of AGG, larger CGG repeat size (in men), and elevatedASFMR1-TV2 level (in women) were strongly associated with FXTAS compared with NC and PMC (combined).ConclusionsThis study found elevated levels ofASFMR1-TV2and loss of AGG interruptions in both men and women with FXTAS. Future studies will be needed to determine whether these variables can provide useful diagnostic or predictive information.

scholarly journals CGG-repeat length and neuropathological and molecular correlates in a mouse model for fragile X-associated tremor/ataxia syndrome

2008 ◽  
Vol 107 (6) ◽  
pp. 1671-1682 ◽  
Author(s):  
Judith R. Brouwer ◽  
Karin Huizer ◽  
Lies-Anne Severijnen ◽  
Renate K. Hukema ◽  
Robert F. Berman ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fragile X ◽  
Repeat Length ◽  
Cgg Repeat ◽  
Ataxia Syndrome

scholarly journals CGG Repeat-Associated Translation Mediates Neurodegeneration in Fragile X Tremor Ataxia Syndrome

Neuron ◽  
2013 ◽  
Vol 79 (2) ◽  
pp. 402 ◽  
Author(s):  
Peter K. Todd ◽  
Seok Yoon Oh ◽  
Amy Krans ◽  
Fang He ◽  
Chantal Sellier ◽  
...  
Keyword(s):  
Fragile X ◽  
Cgg Repeat ◽  
Ataxia Syndrome

scholarly journals CGG Repeat-Associated Translation Mediates Neurodegeneration in Fragile X Tremor Ataxia Syndrome

Neuron ◽  
2013 ◽  
Vol 78 (3) ◽  
pp. 440-455 ◽  
Author(s):  
Peter K. Todd ◽  
Seok Yoon Oh ◽  
Amy Krans ◽  
Fang He ◽  
Chantal Sellier ◽  
...  
Keyword(s):  
Fragile X ◽  
Cgg Repeat ◽  
Ataxia Syndrome

scholarly journals Human Cerebral Cortex Proteome of Fragile X-Associated Tremor/Ataxia Syndrome

2021 ◽  
Vol 7 ◽  
Author(s):  
Katharine Nichole Holm ◽  
Anthony W. Herren ◽  
Sandra L. Taylor ◽  
Jamie L. Randol ◽  
Kyoungmi Kim ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Structural Integrity ◽  
Rna Binding ◽  
Neurodegenerative Disorder ◽  
Fragile X ◽  
Protein Abundance ◽  
Cgg Repeat ◽  
Phosphoserine Aminotransferase ◽  
Brain Volume Loss ◽  
Ataxia Syndrome

Background: Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder associated with premutation CGG-repeat expansions (55–200 repeats) in the 5′ non-coding portion of the fragile X mental retardation 1 (FMR1) gene. Core features of FXTAS include progressive tremor/ataxia, cognitive decline, variable brain volume loss, and white matter disease. The principal histopathological feature of FXTAS is the presence of central nervous system (CNS) and non-CNS intranuclear inclusions.Objective: To further elucidate the molecular underpinnings of FXTAS through the proteomic characterization of human FXTAS cortexes.Results: Proteomic analysis of FXTAS brain cortical tissue (n = 8) identified minor differences in protein abundance compared to control brains (n = 6). Significant differences in FXTAS relative to control brain predominantly involved decreased abundance of proteins, with the greatest decreases observed for tenascin-C (TNC), cluster of differentiation 38 (CD38), and phosphoserine aminotransferase 1 (PSAT1); proteins typically increased in other neurodegenerative diseases. Proteins with the greatest increased abundance include potentially novel neurodegeneration-related proteins and small ubiquitin-like modifier 1/2 (SUMO1/2). The FMRpolyG peptide, proposed in models of FXTAS pathogenesis but only identified in trace amounts in the earlier study of FXTAS inclusions, was not identified in any of the FXTAS or control brains in the current study.Discussion: The observed proteomic shifts, while generally relatively modest, do show a bias toward decreased protein abundance with FXTAS. Such shifts in protein abundance also suggest altered RNA binding as well as loss of cell–cell adhesion/structural integrity. Unlike other neurodegenerative diseases, the proteome of end-stage FXTAS does not suggest a strong inflammation-mediated degenerative response.

Intrafamilial variability in fragile X-associated tremor/ataxia syndrome

2006 ◽  
Vol 21 (1) ◽  
pp. 98-102 ◽  
Author(s):  
Nils Peters ◽  
Christoph Kamm ◽  
Friedrich Asmus ◽  
Elke Holinski-Feder ◽  
Eduard Kraft ◽  
...  
Keyword(s):  
Fragile X ◽  
Intrafamilial Variability ◽  
Ataxia Syndrome

scholarly journals CGG repeat RNA G-quadruplexes interact with FMRpolyG to cause neuronal dysfunction in fragile X-related tremor/ataxia syndrome

2021 ◽  
Vol 7 (3) ◽  
pp. eabd9440
Author(s):  
Sefan Asamitsu ◽  
Yasushi Yabuki ◽  
Susumu Ikenoshita ◽  
Kosuke Kawakubo ◽  
Moe Kawasaki ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Aminolevulinic Acid ◽  
Fragile X ◽  
Protoporphyrin Ix ◽  
Neuronal Dysfunction ◽  
Cgg Repeat ◽  
Repeat Expansions ◽  
Ataxia Syndrome ◽  
And Behavior ◽  
Ran Translation

Fragile X-related tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease caused by CGG triplet repeat expansions in FMR1, which elicit repeat-associated non-AUG (RAN) translation and produce the toxic protein FMRpolyG. We show that FMRpolyG interacts with pathogenic CGG repeat-derived RNA G-quadruplexes (CGG-G4RNA), propagates cell to cell, and induces neuronal dysfunction. The FMRpolyG polyglycine domain has a prion-like property, preferentially binding to CGG-G4RNA. Treatment with 5-aminolevulinic acid, which is metabolized to protoporphyrin IX, inhibited RAN translation of FMRpolyG and CGG-G4RNA–induced FMRpolyG aggregation, ameliorating aberrant synaptic plasticity and behavior in FXTAS model mice. Thus, we present a novel therapeutic strategy to target G4RNA prionoids.

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