Yale researchers find a cause and possible treatment for Fragile X

Fragile X syndrome — a disorder of the X chromosome — is the leading cause of autism and the primary genetic driver of intellectual disability.
Source: Yale Science and Health News - Category: Universities & Medical Training Source Type: news

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Barrett LE Abstract Fragile X mental retardation 1 (FMR1) encodes the RNA binding protein FMRP. Loss of FMRP drives Fragile X syndrome (FXS), the leading inherited cause of intellectual disability and a leading monogenic cause of autism. While cortical hyperexcitability is a hallmark of FXS, the reported phenotypes and underlying mechanisms, including alterations in synaptic transmission and ion channel properties, are heterogeneous and at times contradictory. Here, we report the generation of new isogenic FMR1y/+ and FMR1y/- human pluripotent stem cell (hPSC) lines using CRISPR-Cas9 to facilitate the study of ho...
Source: Developmental Biology - Category: Biology Authors: Tags: Dev Biol Source Type: research
Fragile X syndrome (FXS) is the most common identifiable cause of inherited intellectual disability and autism spectrum conditions, and is associated with a range of physical, cognitive and behavioural characteristics. Alongside intellectual disability, heightened rates of autism spectrum disorder, anxiety disorders, attention-deficit-hyperactivity disorder, self-injury and aggression are reported. Timely identification of FXS as well as assessments of common co-morbid psychological conditions and underlying health problems are essential to ensure individuals with FXS receive appropriate support.
Source: Paediatrics and Child Health - Category: Pediatrics Authors: Tags: Personal practice Source Type: research
FMR1 has a dynamic trinucleotide CGG repeat element in the promotor region, and when the CGG repeat expands to a repeat length above 200 during maternal transmission, FMR1 becomes methylated and its gene and protein expressions are silenced. Deficiency of the FMR1 protein product FMRP causes fragile X syndrome (FXS), the most commonly inherited form of intellectual disability and autism spectrum disorder. FXS is associated with a wide spectrum of comorbidities, including seizures, sensory hypersensitivity, hyperactivity, impulsivity, anxiety, and impaired learning (1).
Source: Biological Psychiatry - Category: Psychiatry Authors: Tags: Early Career Investigator Commentary Source Type: research
We report a case of schizophrenia in a male patient diagnosed with Fragile X syndrome. The patient has been followed up for a period of 3 years. The diagnostic and management challenges are discussed. This is a unique case of schizophrenia in Fragile X syndrome. We discuss the common molecular pathways to the expression of both schizophrenia and Fragile X syndrome. This is the first case report of schizophrenia in a patient with diagnosis of Fragile X syndrome in Australia.
Source: Psychiatric Genetics - Category: Genetics & Stem Cells Tags: Brief Report Source Type: research
Publication date: Available online 13 May 2020Source: Research in Developmental DisabilitiesAuthor(s): Brianna Ruth Doherty, Elena Longhi, Victoria Cole, Annette Karmiloff-Smith, Kim Cornish, Gaia Scerif
Source: Research in Developmental Disabilities - Category: Disability Source Type: research
AbstractFragile X syndrome (FXS) is the most common single gene cause of autism and intellectual disabilities. Humans with FXS exhibit increased anxiety, sensory hypersensitivity, seizures, repetitive behaviors, cognitive inflexibility, and social behavioral impairments. The main purpose of this review is to summarize developmental studies of FXS in humans and in the mouse model, theFmr1 knockout mouse. The literature presents considerable evidence that a number of early developmental deficits can be identified and that these early deficits chart a course of altered developmental experience leading to symptoms well charact...
Source: Journal of Neurodevelopmental Disorders - Category: Neurology Source Type: research
In this study, we examined several white matter regions in the maleFmr1 KO mouse brain compared to male wild-type (WT) mice at postnatal days (PND) 18, 21, 30, and 60, which coincide with critical stages of myelination and postnatal brain development. White matter volume, T2 relaxation time, and magnetization transfer ratio (MTR) were measured using magnetic resonance imaging and myelin content was determined with histological staining of myelin. Differences in the developmental accumulation of white matter and myelin betweenFmr1 KO and WT mice were observed in the corpus callosum, external and internal capsules, cerebral ...
Source: Developmental Neuroscience - Category: Neuroscience Source Type: research
Discussion Fragile X syndrome (FXS) was first clinically described in 1943 by Martin-Bell and in 1969 Lubs found a fragility at the terminal end of the X chromosome. In 1991, three different research groups independently cloned the mutation for the FMR1 gene (Fragile X mental retardation type 1) which has a CGG triplet expansion. The FMR1 gene codes for the FMR protein which is a major regulator of synaptic plasticity and is expressed in the brain and spermatogonia mainly but many other tissues during fetal and early neonatal development. The number of triplets and methylation correlates with clinical expression (increased...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Fragile X syndrome (FXS) is the most frequent cause of inherited intellectual disability and the most commonly identified monogenic cause of autism. Recent studies have shown that long-term pathological conseq...
Source: BMC Neurology - Category: Neurology Authors: Tags: Research 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
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