Study: Disease-causing repeats help human neurons function

(Michigan Medicine - University of Michigan) Researchers found that repeats in the gene that causes Fragile X Syndrome normally regulate how and when proteins are made in neurons.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news

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Usdin In fragile X syndrome (FXS), expansion of a CGG repeat tract in the 5′-untranslated region of the FMR1 gene to >200 repeats causes transcriptional silencing by inducing heterochromatin formation. Understanding the mechanism of FMR1 silencing is important as gene reactivation is a potential treatment approach for FXS. To date, only the DNA demethylating drug 5-azadeoxycytidine (AZA) has proved effective at gene reactivation; however, this drug is toxic. The repressive H3K9 methylation mark is enriched on the FMR1 gene in FXS patient cells and is thus a potential druggable target. However, its cont...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research
RNA-binding proteins (RNA-BPs) play critical roles in development and disease to regulate gene expression. However, genome-wide identification of their targets in primary human cells has been challenging. Here, we applied a modified CLIP-seq strategy to identify genome-wide targets of the FMRP translational regulator 1 (FMR1), a brain-enriched RNA-BP, whose deficiency leads to Fragile X Syndrome (FXS), the most prevalent inherited intellectual disability. We identified FMR1 targets in human dorsal and ventral forebrain neural progenitors and excitatory and inhibitory neurons differentiated from human pluripotent stem cells...
Source: Genome Research - Category: Genetics & Stem Cells Authors: Tags: RESEARCH Source Type: research
NIH-funded test seeks to increase participation of individuals with Fragile X in clinical trials.
Source: National Institutes of Health (NIH) News Releases - Category: American Health Source Type: news
AbstractBackgroundThe evaluation of treatment efficacy for individuals with fragile X syndrome (FXS) or intellectual disability (ID) more generally has been hampered by the lack of adequate outcome measures. We evaluated expressive language sampling (ELS) as a procedure for generating outcome measures for treatment research in FXS. We addressed: (a) feasibility, (b) practice effects over two administrations, (c) test-retest reliability over the repeated administrations, and (d) construct validity. We addressed these issues for the full sample as well as for subgroups defined by age, IQ, and ASD status.MethodsParticipants w...
Source: Journal of Neurodevelopmental Disorders - Category: Neurology Source Type: research
(University of California - Davis Health) Expressive language sampling yielded five language-related outcome measures that may be useful for treatment studies in intellectual disabilities, especially fragile X syndrome. The measures were generally valid and reliable across the range of ages, IQs and autism symptom severity of participants. According to the study, led by UC Davis researchers and funded by NIH, the measures are also functional in supporting treatments that can improve language, providing far reaching benefits for individuals with intellectual disabilities.
Source: EurekAlert! - Social and Behavioral Science - Category: International Medicine & Public Health Source Type: news
Condition:   Fragile X Syndrome (FXS) Intervention:   Drug: 18F-FTC-146 Sponsor:   Stanford University Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Contributors : Elisa Donnard ; Manuel GarberSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusDespite advances in understanding the pathophysiology of Fragile X syndrome (FXS), its molecular bases are still poorly understood. We performed single cell RNA-seq from the cortex of both Fmr1-knock out (Fmr1-KO) and wild type (WT) FVB animals at postnatal day 5. After stringent filtering, we obtained 18,393 cells for which we detected an average of 1,778 genes and 3,988 transcripts. We identified a total of 18 distinct populations, these include vascular cells (endothelial cells and pericytes...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Conditions:   Fragile X Syndrome (FXS);   Idiopathic Intellectual Developmental Disorder (IDD) Intervention:   Drug: [18F]flumazenil Sponsor:   Stanford University Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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