BACKGROUND Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and is also associated with autism spectrum disorders. Previous studies implicated BKCa channels in the neuropathogenesis of FXS, but the main question was whether pharmacological BKCa stimulation would be able to rescue FXS neurobehavioral phenotypes. METHODS AND RESULTS We used a selective BKCa ...

Fragile X syndrome (FXS) accounts for about one-half of cases of X-linked intellectual disability and is the most common monogenic cause of mental impairment. Reproductive options for the FXS carriers include preimplantation genetic diagnosis (PGD). However, this strategy is considered by some centers as wasteful owing to the high prevalence of premature ovarian failure in FXS carriers and the ...

Impairments in the social use of language, or pragmatics, constitute a core characteristic of autism. Problems with pragmatic language have also been documented in fragile X syndrome (FXS), a monogenic condition that is the most common known genetic cause of autism. Evidence suggests that social cognitive ability, or theory of mind, may also be impaired in both conditions, and in autism, may im...

The purpose of this article is to provide an overview of the behavioral phenotype of FMR1 mutations, including fragile X syndrome (FXS) in order to better understand the clinical involvement of individuals affected by mutations in this gene. FXS is associated with a wide range of intellectual and behavioral problems, some relatively mild and others quite severe. FXS is the most common cause of ...

The PI3K enhancer PIKE links PI3K catalytic subunits to group 1 metabotropic glutamate receptors (mGlu1/5) and activates PI3K signaling. The roles of PIKE in synaptic plasticity and the etiology of mental disorders are unknown. Here, we show that increased PIKE expression is a key mediator of impaired mGlu1/5-dependent neuronal plasticity in mouse and fly models of the inherited intellectual di...

The Fragile X mental retardation protein (FMRP) regulates neuronal RNA metabolism, and its absence or mutations leads to the Fragile X syndrome (FXS). The β-amyloid precursor protein (APP) is involved in Alzheimer's disease, plays a role in synapse formation, and is upregulated in intellectual disabilities. Here, we show that during mouse synaptogenesis and in human FXS fibroblasts, a dual dysr...

BACKGROUND/AIMS Despite the advances in understanding visuo-spatial processing in developmental disorders such as ASD and fragile X syndrome (FXS), less is known about the profile of those with a comorbid diagnosis, or the role of within-disorder disparities between individuals across the ASD spectrum. METHODS AND PROCEDURES Using a developmental trajectory approach, we tested 5 groups of chi...

Fragile X syndrome (FXS) is characterised by hyper-reactivity, autistic tendencies and social anxiety. It has been hypothesised that the FXS social phenotype is secondary to a generalised hyper-reactivity that leads to social avoidance. No study, however, has investigated whether hyperarousal in FXS is generalised or more specific to socially salient information. We recorded skin conductance re...

Fragile X syndrome (FXS) patients present neuronal alterations that lead to severe intellectual disability, but the underlying neuronal circuit mechanisms are poorly understood. An emerging hypothesis postulates that reduced GABAergic inhibition of excitatory neurons is a key component in the pathophysiology of FXS. Here, we directly test this idea in a FXS Drosophila model. We show that FXS fl...

The absence of fragile X mental retardation 1 protein (FMRP) results in fragile X syndrome (FXS) that is a common cause of intellectual disability and a variant of autism spectrum disorder. There is evidence that FMRP is involved in neurogenesis. FMRP is widely expressed throughout the embryonic brain development and its expression levels increases during neuronal differentiation. Cortical neur...