Somatic Instability Leading to Mosaicism in Fragile X Syndrome and Associated Disorders: Complex Mechanisms, Diagnostics, and Clinical Relevance.

Fragile X syndrome (FXS) is a genetic condition caused by the inheritance of alleles with >200 CGG repeats in the 5' UTR of the fragile X messenger ribonucleoprotein 1 () gene. These full mutation (FM) alleles are associated with DNA methylation and gene silencing, which result in intellectual disabilities, developmental delays, and social and behavioral issues. Mosaicism for both the size of the CGG repeat tract and the extent of its methylation is commonly observed in individuals with the FM.

Negative effect of treatment with mGluR5 negative allosteric modulator AFQ056 on blood biomarkers in young individuals with Fragile X syndrome.

Background: Fragile X syndrome, with an approximate incidence rate of 1 in 4000 males to 1 in 8000 females, is the most prevalent genetic cause of heritable intellectual disability and the most common monogenic cause of autism spectrum disorder. The full mutation of the Fragile X Messenger Ribonucleoprotein-1 gene, characterized by an expansion of CGG trinucleotide repeats (>200 CGG repeats), leads to fragile X syndrome. Currently, there are no targeted treatments available for fragile X syndrome.

Corrigendum: Pharmacological effects of monoterpene carveol on the neuromuscular system of nematodes and mammals.

[This corrects the article DOI: 10.3389/fphar.2024.

Circadian Rhythm and Sleep Analyses in a Fruit Fly Model of Fragile X Syndrome Using a Video-Based Automated Behavioral Research System.

Fragile X syndrome (FXS) is caused by the full mutation in the gene on the Xq27.3 chromosome region. It is the most common monogenic cause of autism spectrum disorder (ASD) and inherited intellectual disability (ID).

Using a Combination of Novel Research Tools to Understand Social Interaction in the Model for Fragile X Syndrome.

Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism spectrum disorder, is caused by a full mutation (>200 CGG repeats) in the Fragile X Messenger Ribonucleoprotein 1 () gene. Individuals with FXS experience various challenges related to social interaction (SI). Animal models, such as the model for FXS where the only ortholog of human () is mutated, have played a crucial role in the understanding of FXS.

State-of-the-art therapies for fragile X syndrome.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a full mutation (> 200 CGG repeats) in the FMR1 gene. FXS is the leading cause of inherited intellectual disabilities and the most commonly known genetic cause of autism spectrum disorder. Children with FXS experience behavioral and sleep problems, anxiety, inattention, learning difficulties, and speech and language delays.

Pharmacological effects of monoterpene carveol on the neuromuscular system of nematodes and mammals.

The control of parasitic nematode infections relies mostly on anthelmintics. The potential pharmacotherapeutic application of phytochemicals, in order to overcome parasite resistance and enhance the effect of existing drugs, is becoming increasingly important. The antinematodal effects of carveol was tested on the free-living nematode and the neuromuscular preparation of the parasitic nematode .

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on Premutation.

The premutation of the fragile X messenger ribonucleoprotein 1 () gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death.

Activation Ratio Correlates with IQ in Female Carriers of the Premutation.

Carriers of the premutation (PM) allele are at risk of one or more clinical conditions referred to as FX premutation-associated conditions (FXPAC). Since the gene is on the X chromosome, the activation ratio (AR) may impact the risk, age of onset, progression, and severity of these conditions. The aim of this study was to evaluate the reliability of AR measured using different approaches and to investigate potential correlations with clinical outcomes.

as a Model to Study Fragile X-Associated Disorders.

Fragile X syndrome (FXS) is a global neurodevelopmental disorder caused by the expansion of CGG trinucleotide repeats (≥200) in the Fragile X Messenger Ribonucleoprotein 1 () gene. FXS is the hallmark of Fragile X-associated disorders (FXD) and the most common monogenic cause of inherited intellectual disability and autism spectrum disorder. There are several animal models used to study FXS.

Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers.

The fragile X premutation carrier state (PM) (55-200 CGG repeats in the fragile X messenger ribonucleoprotein 1, gene) is associated with several conditions, including fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor ataxia (FXTAS), with current literature largely primarily investigating older PM individuals. The aim of this study was to identify the prevalence of fragile X-associated neurodevelopmental disorders (FXAND) in a sample of young PM individuals. This was a retrospective study conducted through a medical record review of PM individuals who were seen either for clinical concerns (probands, 45.

Autism spectrum disorder in the fragile X premutation state: possible mechanisms and implications.

There is increasing recognition of the heterogeneity of origin of cases of autism spectrum disorder (ASD) with multiple forms of ASD having been identified over the decades. Among these, a genetic etiology can be identified in 20-40% of cases when a full genetic work-up is completed. The Fragile X premutation state (characterized by the presence of 55-200 CGG repeats in the FMR1 gene) is a relatively newly identified disease state that has since been associated with several disorders including fragile X-associated tremor ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI) and most recently, fragile X-associated neurodevelopmental disorders (FXAND) which commonly includes anxiety and depression.

Fragile X Syndrome: From Molecular Aspect to Clinical Treatment.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the full mutation as well as highly localized methylation of the fragile X mental retardation 1 () gene on the long arm of the X chromosome. Children with FXS are commonly co-diagnosed with Autism Spectrum Disorder, attention and learning problems, anxiety, aggressive behavior and sleep disorder, and early interventions have improved many behavior symptoms associated with FXS. In this review, we performed a literature search of original and review articles data of clinical trials and book chapters using MEDLINE (1990-2021) and ClinicalTrials.

Raising Knowledge and Awareness of Fragile X Syndrome in Serbia, Georgia, and Colombia: A Model for Other Developing Countries?

Fragile X syndrome is the most common monogenetic cause of inherited intellectual disability and syndromic autism spectrum disorder. Fragile X syndrome is caused by an expansion (full mutation ≥200 CGGs repeats, normal 10-45 CGGs) of the fragile X mental retardation 1 () gene, epigenetic silencing of the gene, which leads to reduction or lack of the gene's product: the fragile X mental retardation protein. In this cross-sectional study, we assessed general and pharmacotherapy knowledge (GK and PTK) of fragile X syndrome and satisfaction with education in neurodevelopmental disorders (NDDs) among senior medical students in Serbia (N=348), Georgia (N=112), and Colombia (N=58).

Sleep problems in fragile X syndrome: Cross-sectional analysis of a large clinic-based cohort.

Fragile X syndrome (FXS), the leading cause of inherited intellectual disability and autism spectrum disorder, is associated with multiple neurobehavioral abnormalities including sleep difficulties. Nonetheless, frequency, severity, and consequences of sleep problems are still unclear. The Fragile X Online Registry with Accessible Research Database (FORWARD-version-3), including Clinician Report and Parent Report forms, was analyzed for frequency, severity, relationship with behavioral problems, and impact of sleep difficulties in a mainly pediatric cohort.

A Genotype-Phenotype Study of High-Resolution Nucleic Acid and Protein Analyses in Fragile X Patients with Neurobehavioral Assessments.

Fragile X syndrome (FXS) is caused by silencing of the gene, which encodes a protein with a critical role in synaptic plasticity. The molecular abnormality underlying silencing, CGG repeat expansion, is well characterized; however, delineation of the pathway from DNA to RNA to protein using biosamples from well characterized patients with FXS is limited. Since FXS is a common and prototypical genetic disorder associated with intellectual disability (ID) and autism spectrum disorder (ASD), a comprehensive assessment of the DNA-RNA-protein pathway and its correlations with the neurobehavioral phenotype is a priority.

Rapidly Progressing Neurocognitive Disorder in a Male with FXTAS and Alzheimer's Disease.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that usually begins in the early 60s and affects carriers of premutation expansion (55-200 CGG repeats) of the fragile X mental retardation 1 () gene. Additional disorders can co-occur with FXTAS including Alzheimer's disease (AD). Here we discuss a case report of a male with 67 CGG repeats in who had mild late-onset FXTAS symptoms followed by neurocognitive disorder symptoms consistent with AD.

Association between IQ and FMR1 protein (FMRP) across the spectrum of CGG repeat expansions.

Fragile X syndrome, the leading heritable form of intellectual disability, is caused by hypermethylation and transcriptional silencing of large (CGG) repeat expansions (> 200 repeats) in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene. As a consequence of FMR1 gene silencing, there is little or no production of FMR1 protein (FMRP), an important element in normal synaptic function. Although the absence of FMRP has long been known to be responsible for the cognitive impairment in fragile X syndrome, the relationship between FMRP level and cognitive ability (IQ) is only imprecisely understood.

New Targeted Treatments for Fragile X Syndrome.

Fragile X Syndrome (FXS) is the most common cause of inherited intellectual disability with prevalence rates estimated to be 1:5,000 in males and 1:8,000 in females. The increase of >200 Cytosine Guanine Guanine (CGG) repeats in the 5' untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene results in transcriptional silencing on the FMR1 gene with a subsequent reduction or absence of fragile X mental retardation protein (FMRP), an RNA binding protein involved in the maturation and elimination of synapses. In addition to intellectual disability, common features of FXS are behavioral problems, autism, language deficits and atypical physical features.

Cognitive and behavioral improvement in adults with fragile X syndrome treated with metformin-two cases.

Background: The majority of individuals with fragile X syndrome (FXS) have intellectual disability, behavioral problems, autism, and language deficits. IQ typically declines with age in boys with the full mutation. The results of preclinical studies demonstrated that metformin, a biguanide used to treat type 2 diabetes, rescues multiple phenotypes of FXS in both Drosophila and mouse models.

Fragile X-Associated Neuropsychiatric Disorders (FXAND).

Fragile X syndrome (FXS) is caused by the full mutation (>200 CGG repeats) in the Fragile X Mental Retardation 1 () gene. It is the most common inherited cause of intellectual disability (ID) and autism. This review focuses on neuropsychiatric disorders frequently experienced by premutation carriers with 55 to 200 CGG repeats and the pathophysiology involves elevated mRNA levels, which is different from the absence or deficiency of fragile X mental retardation protein (FMRP) seen in FXS.