Mosaicism in Fragile X syndrome: A family case series

Saldarriaga, Wilmar; González-Teshima, Laura Yuriko; Forero-Forero, José Vicente; Tang, Han; Tassone, Flora

doi:10.1177/1744629521995346

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…In contrast, in the methylation mosaicism some individuals with the full mutation silence the FMR1 gene in some cells and not in others 30 . In those affected by Fragile X syndrome with mosaicism, different amounts of FMRP are produced between cell populations and these individuals have a less severe phenotype 33 .…”

Section: The Fmr1 Genementioning

confidence: 99%

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Fragile X syndrome in children

Acero-Garcés,

Saldarriaga,

Cabal-Herrera

et al. 2023

Colomb Med

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Fragile X syndrome is caused by the expansion of CGG triplets in the FMR1 gene, which generates epigenetic changes that silence its expression. The absence of the protein coded by this gene, FMRP, causes cellular dysfunction, leading to impaired brain development and functional abnormalities. The physical and neurologic manifestations of the disease appear early in life and may suggest the diagnosis. However, it must be confirmed by molecular tests. It affects multiple areas of daily living and greatly burdens the affected individuals and their families. Fragile X syndrome is the most common monogenic cause of intellectual disability and autism spectrum disorder; the diagnosis should be suspected in every patient with neurodevelopmental delay. Early interventions could improve the functional prognosis of patients with Fragile X syndrome, significantly impacting their quality of life and daily functioning. Therefore, healthcare for children with Fragile X syndrome should include a multidisciplinary approach.

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Section: The Fmr1 Genementioning

confidence: 99%

“…En contraste, en el mosaicismo de metilación algunos individuos con la mutación silencian el gen FMR1 en unas células y no en otras 30 . En los afectados por el síndrome de X frágil con mosaicismo se producen diferentes cantidades de FMRP entre poblaciones celulares, lo que genera un fenotipo menos grave 33 .…”

Section: Gen Fmr1unclassified

Fragile X syndrome in children

Acero-Garcés,

Saldarriaga,

Cabal-Herrera

et al. 2023

Colomb Med

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“…Assessing local changes in brain activity using electroencephalography (EEG) or magnetoencephalography (MEG) or functional magnetic resonance imaging (fMRI), both at baseline (e.g., before starting administering the drug) and after intervention, could provide significant insights into that. In addition, it will be important to consider the presence of mosaicism in the brain which could impact the drug-phenotype interactions ( 172 , 173 ), although, at this time, its assessment is not possible within the brain in humans.…”

Section: A New Approachmentioning

confidence: 99%

Phenotypic Trade-Offs: Deciphering the Impact of Neurodiversity on Drug Development in Fragile X Syndrome

et al. 2021

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Fragile X syndrome (FXS) is the most common single-gene cause of intellectual disability and autism spectrum disorder. Individuals with FXS present with a wide range of severity in multiple phenotypes including cognitive delay, behavioral challenges, sleep issues, epilepsy, and anxiety. These symptoms are also shared by many individuals with other neurodevelopmental disorders (NDDs). Since the discovery of the FXS gene, FMR1, FXS has been the focus of intense preclinical investigation and is placed at the forefront of clinical trials in the field of NDDs. So far, most studies have aimed to translate the rescue of specific phenotypes in animal models, for example, learning, or improving general cognitive or behavioral functioning in individuals with FXS. Trial design, selection of outcome measures, and interpretation of results of recent trials have shown limitations in this type of approach. We propose a new paradigm in which all phenotypes involved in individuals with FXS would be considered and, more importantly, the possible interactions between these phenotypes. This approach would be implemented both at the baseline, meaning when entering a trial or when studying a patient population, and also after the intervention when the study subjects have been exposed to the investigational product. This approach would allow us to further understand potential trade-offs underlying the varying effects of the treatment on different individuals in clinical trials, and to connect the results to individual genetic differences. To better understand the interplay between different phenotypes, we emphasize the need for preclinical studies to investigate various interrelated biological and behavioral outcomes when assessing a specific treatment. In this paper, we present how such a conceptual shift in preclinical design could shed new light on clinical trial results. Future clinical studies should take into account the rich neurodiversity of individuals with FXS specifically and NDDs in general, and incorporate the idea of trade-offs in their designs.

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Fragile X syndrome

2023

Cases in Laboratory Genetics and Genomics (LGG) Practice

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Mosaicism in Fragile X syndrome: A family case series

Cited by 4 publications

References 19 publications

Fragile X syndrome in children

Fragile X syndrome in children

Phenotypic Trade-Offs: Deciphering the Impact of Neurodiversity on Drug Development in Fragile X Syndrome

Fragile X syndrome

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