GEO DataSets

(Submitter supplied) Fragile X syndrome (FXS) is one of the most prevalent inherited intellectual disabilities. The patients carry the expansion of over 200 CGG repeats located at the 5′ untranslated region of fragile X mental retardation 1 (FMR1). As a result, the FMR1 promoter becomes hypermethylated leading to decreased or absent expression of its encoded RNA-binding protein fragile X mental retardation protein (FMRP). more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

8 Samples

Download data: TXT

(Submitter supplied) Fragile X syndrome (FXS) is caused by transcriptional silencing of the FMR1 gene during embryonic development with the consequent loss of the encoded fragile X mental retardation protein (FMRP). The pathological mechanisms of FXS have been extensively studied using the Fmr1-knockout mouse, and the findings suggest important roles for FMRP in synaptic plasticity and proper functioning of neural networks. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL21185

4 Samples

Download data: TXT

(Submitter supplied) Fragile X syndrome (FXS) is caused by the absence of the fragile X mental retardation protein (FMRP). We have previously generated FXS-induced pluripotent stem cells (iPSCs) from patients' fibroblasts. In this study, we aimed at unraveling the molecular phenotype of the disease. Our data revealed aberrant regulation of neural differentiation and axon guidance genes in FXS-derived neurons, which are regulated by the RE-1 silencing transcription factor (REST). more...

Organism:

Homo sapiens; synthetic construct

Type:

Non-coding RNA profiling by array; Expression profiling by array

Platforms:

GPL6244 GPL8786

18 Samples

Download data: CEL

(Submitter supplied) Transcriptional silencing of the FMR1 gene in fragile X syndrome (FXS) leads to loss of the RNA-binding protein, FMRP. In addition to its well-established role of regulating protein synthesis, emerging evidence suggests that FMRP acts to coordinate proliferation and differentiation during early neural development. However, whether translational control by FMRP drives critical cellular events of fate specification and developmental transitions in the developing human brain remains unknown. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL20301 GPL18573

12 Samples

Download data: FPKM_TRACKING, TXT

(Submitter supplied) Fragile X syndrome (FXS) is a rare disease but is the most common form of inherited intellectual disability and a leading cause of autism. FXS is due to the absence of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein mainly involved in translational control. Even if this molecular defect is known, no specific therapy is available for FXS. The first alteration observed in the brain of FXS patients and of Fmr1 KO mice, model for FXS, is represented by an abnormal dendritic morphology that is associated with an altered synaptic plasticity. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL4134

4 Samples

Download data: GPR

(Submitter supplied) FXS (Fragile X Syndrome), a leading monogenic cause of intellectual disability and autism spectrum disorder, is caused by an expansion of a CGG repeat in the 5′-UTR of the FMR1 (Fragile X Mental Retardation-1) gene. While current studies of FXS have focused on the effects of Fragile X Mental Retardation Protein (FMRP) loss in excitatory neurons, evidence suggests that GABAergic inhibitory networks are also affected in FXS. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

14 Samples

Download data: CLOUPE, TAR

(Submitter supplied) We report the generation of isogenic hPSC model of FXS and characterize the neurodevelopmental capacity of these cells, performed transcriptome profiling in FXS neurons and identified key pathways

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

24 Samples

Download data: CSV, TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Methylation profiling by high throughput sequencing

Platform:

GPL16791

35 Samples

Download data: BW, COV, TXT, WIG

(Submitter supplied) Fragile X syndrome (FXS), the most common genetic form of intellectual disability in male, is caused by silencing of the FMR1 gene by hypermethylation of the CGG expansion mutation in the 5’UTR region of FMR1 in FXS patients. Here, we applied recently developed DNA methylation editing tools to reverse this hypermethylation event. Targeted demethylation of the CGG expansion by dCas9-Tet1/sgRNA switched the heterochromatin status of the upstream FMR1 promoter to an active chromatin state restoring a persistent expression of FMR1 in FXS iPSCs. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

7 Samples

Download data: TXT

(Submitter supplied) Fragile X syndrome (FXS), the most common genetic form of intellectual disability in male, is caused by silencing of the FMR1 gene by hypermethylation of the CGG expansion mutation in the 5’UTR region of FMR1 in FXS patients. Here, we applied recently developed DNA methylation editing tools to reverse this hypermethylation event. Targeted demethylation of the CGG expansion by dCas9-Tet1/sgRNA switched the heterochromatin status of the upstream FMR1 promoter to an active chromatin state restoring a persistent expression of FMR1 in FXS iPSCs. more...

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL16791

4 Samples

Download data: COV

(Submitter supplied) Fragile X syndrome (FXS), the most common genetic form of intellectual disability in male, is caused by the silence of FMR1. Hypermethylation of the CGG expansion mutation in the 5’UTR region of FMR1 in FXS patients was thought to epigenetically silence FMR1. Here, we applied our previously developed DNA methylation editing tool to reverse this hypermethylation event. Targeted demethylation of the CGG expansion by dCas9-Tet1/gRNA switched the heterochromatin status of the FMR1 promoter to an active chromatin status and subsequently restored FMR1 expression in FXS iPSCs. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

18 Samples

Download data: WIG

(Submitter supplied) Fragile X syndrome (FXS), the most common genetic form of intellectual disability in male, is caused by the silence of FMR1. Hypermethylation of the CGG expansion mutation in the 5’UTR region of FMR1 in FXS patients was thought to epigenetically silence FMR1. Here, we applied our previously developed DNA methylation editing tool to reverse this hypermethylation event. Targeted demethylation of the CGG expansion by dCas9-Tet1/gRNA switched the heterochromatin status of the FMR1 promoter to an active chromatin status and subsequently restored FMR1 expression in FXS iPSCs. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

6 Samples

Download data: BW

(Submitter supplied) Fragile X syndrome (FXS) is caused primarily by a CGG repeat expansion mutation in the FMR1 gene that triggers its epigenetic silencing. In order to investigate the role of different epigenetic regulatory layers in the silencing of FMR1 expression, we tested a collection of epigenetic modulators for the ability to reactivate the FMR1 locus. While inhibitors of DNA methylatransferase induced the highest levels of FMR1 mRNA expression, a combination of a DNMT inhibitor and a novel epigenetic agent was able to potentiate the effect of reactivating treatment. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: TXT

(Submitter supplied) Isogenic hESC clones with and without the FX mutation that share the same genetic background were in vitro differentiated into neurons. FX neurons present delayed neuronal development and maturation with full FMRP silencing. Following enrichment of neurons in the culture by MACS, transcriptome analysis by RNA sequencing at different time points during differentiation demonstrated dysregulation of the TGFβ/BMP signaling pathway and genes related to the extracellular matrix. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

18 Samples

Download data: TXT

(Submitter supplied) The goal of this study was to define molecular overlap between Down syndrome and Fragile X syndrome using human pluripotent stem cells (hPSCs) and in vitro derived glutamatergic neurons.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

40 Samples

Download data: CSV

(Submitter supplied) Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP), a translation-inhibitor RNA binding protein. The impact of FMRP-deficiency on neural function is widespread, including its regulation of adult neural stem cell (aNSC) differentiation. To assess FMRP activity, we performed ribosome profiling of aNSCs from normal and Fmr1 knockout mice, which revealed diverse gene expression changes at the mRNA and translation levels. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL19057

16 Samples

Download data: TXT, XLSX

(Submitter supplied) We found that the previously published Fmr1 knockout rat model of FXS expresses an Fmr1 transcript with an in-frame deletion of exon 8, which encodes for the K-homology (KH) RNA-binding domain, KH1. We observed that the deletion of exon 8 in 10 male rats within the medial prefrontal cortex (mPFC) led to transcriptional alterations compared to 12 WT rats using RNAseq. Additionally, we used weighted gene co-expression network analysis to generate 23 modules specific to the mPFC with tissue from 35 WT rat samples.

Organism:

Rattus norvegicus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL10669

45 Samples

Download data: XLSX

(Submitter supplied) We identified FMRP-bound RNAs in hPSC (human pluripotent stem cells)-differentiated forebrain neuroprogenitors (NPCs) and neurons using crosslinking immunoprecipitation (CLIP) coupled to high-throughput sequencing. We examined transcriptomic and proteomic changes in FMRP-KO NPCs and neurons.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL16791

60 Samples

Download data: XLSX

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL24676 GPL18573

57 Samples

Download data: BROADPEAK, NARROWPEAK

(Submitter supplied) Aberrant alternative splicing of mRNAs results in dysregulated gene expression in multiple neurological disorders. Here we show that hundreds of mRNAs are incorrectly expressed and spliced in white blood cells and brain tissue of individuals with fragile X syndrome (FXS). Surprisingly, the FMR1 (Fragile X Messenger Ribonucleoprotein 1) gene is transcribed in >70% of the FXS tissues. In all FMR1 expressing FXS tissues, FMR1 RNA itself is mis-spliced in a CGG expansion-dependent manner to generate the little-known FMR1-217 RNA isoform, which is comprised of FMR1 exon 1 and a pseudo-exon in intron 1. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

15 Samples

Download data: BROADPEAK, NARROWPEAK