Neuroanatomical, molecular genetic, and behavioral correlates of fragile X syndrome

Koukoui, Sophia; Chaudhuri, Avi

doi:10.1016/j.brainresrev.2006.06.001

Cited by 59 publications

(47 citation statements)

References 122 publications

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“…FMRP is therefore crucial for preventing mGluR stimulation leading to excessive AMPAR endocytosis via overactivation of signaling cascades. Patients with fragile X syndrome (FXS) have cognitive deficits that may be due to impairments in synaptic glutamate signaling dependent on key effector and adaptor proteins such as PSD-95 Koukoui and Chaudhuri, 2007). Anxiety and epilepsy symptoms are also elevated in patients with FXS and Fmr1-KO mice, which could be due to disrupted interactions between mGluRs and the short isoform Homer1a (Penagarikano et al, 2007).…”

Section: E Identity Of Newly Synthesized Proteinsmentioning

confidence: 99%

Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms

2009

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Section: E Identity Of Newly Synthesized Proteinsmentioning

confidence: 99%

Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms

2009

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“…hand flapping], hypersensitivity to sensory stimuli, impulsive aggression, or self-injurious hand biting). 11,12 The prevalence of autism within the male FXS population is reported to range from 1.5 ⁄ 100 to 3.3 ⁄ 100, and affected individuals meet all criteria necessary for a diagnosis of autism, including impairments in social interaction, language, and communication, and a pattern of restrictive or repetitive behaviours. 13 FXS is diagnosed in almost 5 ⁄ 100 of individuals with autism.…”

Section: Fragile X Syndromementioning

confidence: 99%

Genetic causes of syndromic and non‐syndromic autism

Çağlayan

2010

Develop Med Child Neuro

102

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Aims Over the past decade, genetic tests have become available for numerous heritable disorders, especially those whose inheritance follows the Mendelian model. Autism spectrum disorders (ASDs) represent a group of developmental disorders with a strong genetic basis. During the past few years, genetic research in ASDs has been successful in identifying several vulnerability loci and a few cytogenetic abnormalities or single‐base mutations implicated in the causation of autism. Method In this study the literature was reviewed to highlight genotype–phenotype correlations between causal gene mutations or cytogenetic abnormalities and behavioural or morphological phenotypes. Results Based on this knowledge, practical information is offered to help clinicians pursue targeted genetic testing of individuals with autism whose clinical phenotype is suggestive of a specific genetic or genomic aetiology. Interpretation Comprehensive research into the molecular mechanism of autism is required to aid the development of disease‐specific targeted therapies. In order to transfer this recently acquired knowledge into clinical practice, it is critical to define a set of phenotypic inclusion criteria that must be met by affected probands to justify their enrolment in a specific genetic testing programme.

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“…The fragile X syndrome (FraX) mental retardation and autism spectrum disorder, which has a prevalence of ~1:4000 males and 1:6000 females, is among the most common inherited neurological diseases (Koukoui and Chaudhuri, 2007;Penagarikano et al, 2007). Loss of fragile X mental retardation protein (FMRP) expression is the sole cause of the disease state.…”

Section: Introductionmentioning

confidence: 99%

Temporal requirements of the fragile X mental retardation protein in the regulation of synaptic structure

2008

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Fragile X syndrome (FraX), caused by the loss-of-function of one gene (FMR1), is the most common inherited form of both mental retardation and autism spectrum disorders. The FMR1 product (FMRP) is an mRNA-binding translation regulator that mediates activity-dependent control of synaptic structure and function. To develop any FraX intervention strategy, it is essential to define when and where FMRP loss causes the manifestation of synaptic defects, and whether the reintroduction of FMRP can restore normal synapse properties. In the Drosophila FraX model, dFMRP loss causes neuromuscular junction (NMJ) synapse overelaboration (overgrowth, overbranching, excess synaptic boutons), accumulation of development-arrested satellite boutons, and altered neurotransmission. We used the Gene-Switch method to conditionally drive dFMRP expression to define the spatiotemporal requirements in synaptic mechanisms. Constitutive induction of targeted neuronal dFMRP at wild-type levels rescues all synaptic architectural defects in Drosophila Fmr1 (dfmr1)-null mutants, demonstrating a presynaptic requirement for synapse structuring. By contrast, presynaptic dFMRP expression does not ameliorate functional neurotransmission defects, indicating a postsynaptic dFMRP requirement. Strikingly, targeted early induction of dFMRP effects nearly complete rescue of synaptic structure defects, showing a primarily early-development role. In addition, acute dFMRP expression at maturity partially alleviates dfmr1-null defects, although rescue is not as complete as either early or constitutive dFMRP expression, showing a modest capacity for late-stage structural plasticity. We conclude that dFMRP predominantly acts early in synaptogenesis to modulate architecture, but that late dFMRP introduction at maturity can weakly compensate for early absence of dFMRP function.

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Neuroanatomical, molecular genetic, and behavioral correlates of fragile X syndrome

Cited by 59 publications

References 122 publications

Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms

Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms

Genetic causes of syndromic and non‐syndromic autism

Temporal requirements of the fragile X mental retardation protein in the regulation of synaptic structure

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