Fragile X syndrome

Garber, Kathryn B.; Visootsak, Jeannie; Warren, Stephen T.

doi:10.1038/ejhg.2008.61

Cited by 369 publications

(293 citation statements)

References 50 publications

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“…It has been hypothesized that in dendrites FMRP locally controls the synthesis of proteins, such as components of the PSD, which regulate both cellular events (1)(2)(3)(4)(5)(6)(7)(8)(9). A crucial question is as follows: which postsynaptic proteins are affected by the loss of FMRP in a quantitative manner?…”

Section: Discussionmentioning

confidence: 99%

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Fragile X Mental Retardation Protein Regulates the Levels of Scaffold Proteins and Glutamate Receptors in Postsynaptic Densities

Schütt¹,

Falley²,

Richter

et al. 2009

Journal of Biological Chemistry

134

115

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In humans, the functional loss of the fragile X mental retardation protein (FMRP) 2 causes the fragile X syndrome (FXS), a severe form of inherited mental retardation (1-4). In the brain of both humans and mice, FMRP deficiency results in a significant change in both dendritic spine morphology and synaptic function (5-9). FMRP is an RNA-binding protein that is thought to act primarily as a repressor of mRNA translation. Among other subcellular regions in neurons, FMRP appears to exercise this control function at postsynaptic sites. It has been hypothesized that in dendrites FMRP locally controls the synthesis of proteins, such as components of the postsynaptic density (PSD), which regulate both dendritic spine morphology and synaptic function (2, 9, 10). The PSD is a complex protein network lying underneath the postsynaptic membrane of excitatory synapses (11-13). It serves to cluster glutamate receptors and cell adhesion molecules, recruit signaling proteins, and anchor these components to the microfilament-based cytoskeleton in dendritic spines. To combine these functions, the central layers of the PSD consist of several scaffold proteins, such as members of the PSD-95, SAPAP/GKAP, and Shank/ProSAP families. Because of their capacity to directly interact with many different PSD components and to regulate the size and shape of dendritic spines, Shanks in particular are assumed to represent master scaffold proteins of the PSD (11). Activity-dependent changes in the PSD composition are thought to represent a molecular basis for most principal brain functions, including learning and memory. Several of these long term synaptic changes and learning paradigms critically depend on dendritic protein synthesis (14 -17). Interestingly, mRNAs encoding some of the central components of the PSD, such as Shank1-3, SAPAP3, PSD-95, and ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor subunits (GluR), are present in dendrites (18 -23).As FMRP has been implicated in the local regulation of mRNA translation at synapses, one crucial question is as follows: which postsynaptic proteins are affected by the loss of FMRP in a quantitative manner and may thus contribute to abnormal dendritic spine morphology and impaired synaptic plasticity? To specifically address this question, we took advan-* This work was supported by the Deutsche Forschungsgemeinschaft Grants Ki488/2-6 (to S. K.) and KR 1321/4-1 (to H.-J. K. and S. K.) and Thyssen-Stiftung Az. 10.05.2.185 (to D. R. and S. K.

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Section: Discussionmentioning

confidence: 99%

“…In the brain of both humans and mice, FMRP deficiency results in a significant change in both dendritic spine morphology and synaptic function (5)(6)(7)(8)(9). FMRP is an RNA-binding protein that is thought to act primarily as a repressor of mRNA translation.…”

mentioning

confidence: 99%

Fragile X Mental Retardation Protein Regulates the Levels of Scaffold Proteins and Glutamate Receptors in Postsynaptic Densities

Schütt¹,

Falley²,

Richter

et al. 2009

Journal of Biological Chemistry

134

115

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“…If indicated, Southern blot was performed by hybridizing the probe StB12.3 to EcoRI-and EagI digested DNA. The sensitivity of both the PCR and Southern blot analyses was 99 % [16][17][18][19].…”

Section: Laboratory Analysesmentioning

confidence: 99%

Evidence of an age-related correlation of ovarian reserve and FMR1 repeat number among women with “normal” CGG repeat status

Gustin

Ding

Desai

et al. 2015

J Assist Reprod Genet

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Purpose The objective of this analysis is to examine the relationship between Fragile X Mental Retardation 1 gene (FMR1) cytosine-guanine-guanine (CGG) repeat number and ovarian reserve, with a particular focus exclusively on the range of CGG repeat number below the premutation (PM) range (<55 CGG repeats). Methods Our study included female patients who underwent assessment of FMR1 CGG repeat number and serum antiMullerian hormone (AMH) in 2009-2014. To examine the association between FMR1 repeat number and serum AMH, we created three summary measures of CGG repeat number for the two alleles-BSum,^BMax,^and BGap^(absolute difference). Using multivariable regression models, controlling for age, we then analyzed the impact of these summary measures on AMH.Results A total of 566 patients were included in our study. Using multivariable regression models, we found that the relationship between CGG repeat number and AMH differed depending on age. Specifically, in younger women, AMH increased by 7-8 % (Sum p<0.01, Max p=0.04) for every 1 unit increase in CGG repeat number. In contrast, starting at age 40, there was a 3 to 5 % decline in AMH for every 1 unit increase in CGG repeat number (Sum p<0.01, Max p=0.04). Conclusions This is the first study to report a statistically significant correlation of ovarian reserve and CGG repeat number in women with <55 CGG repeats. Although these women are generally considered to have a normal phenotype, our data suggest that increasing CGG repeat number within this normal range is associated with a more rapid decline in ovarian reserve.

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“…The average IQ of males with the full mutation is 40 (40). Intellectual and developmental disability occurs in 85% of males and 25% of females.…”

Section: Cognition Deficitsmentioning

confidence: 99%

Fragile X spectrum disorders

Lozano

Rosero²,

Hagerman

2014

IRDR

153

110

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Fragile X syndrome

Cited by 369 publications

References 50 publications

Fragile X Mental Retardation Protein Regulates the Levels of Scaffold Proteins and Glutamate Receptors in Postsynaptic Densities

Fragile X Mental Retardation Protein Regulates the Levels of Scaffold Proteins and Glutamate Receptors in Postsynaptic Densities

Evidence of an age-related correlation of ovarian reserve and FMR1 repeat number among women with “normal” CGG repeat status

Fragile X spectrum disorders

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