The FMR1 Premutation and Fragile X conditions: Expanding the Clinical and Molecular Spectrum

The field of fragile X–associated disorders has rapidly evolved with the discovery of FMR1 premutation–associated conditions, unveiling a complex spectrum of molecular, neurobiological, and clinical consequences that reach far beyond classic fragile X syndrome (FXS). Central to this complexity are the distinctive molecular neuropathological mechanisms triggered by the FMR1 premutation allele- including RNA toxicity, repeat-associated non-AUG (RAN) translation, mitochondrial dysfunction, and DNA damage response- which collectively drive the pathogenesis of fragile X–associated tremor/ataxia syndrome (FXTAS), fragile X–associated primary ovarian insufficiency (FXPOI), fragile X–associated neuropsychiatric disorders (FXAND), in addition to a broader range of clinical involvement including migraine, sleep apnea, immune mediated conditions and hypertension. These findings contrast with the full mutation scenario, where FMR1 gene silencing and loss of FMRP result in the well-characterized features of FXS, the most common inherited cause of intellectual disability and autism.

This Research Topic aims to spotlight cutting-edge research at the interface of molecular neuroscience and clinical translation in FMR1 premutation and FXS conditions. We particularly seek contributions that dissect the molecular neurobiology of premutation disorders, such as investigations of toxic mRNA gain-of-function, dysregulated protein synthesis, RNA-binding protein sequestration, altered synaptic plasticity, mitochondrial deficits, and other pathogenic cascades and studies identifying biomarkers of neuropathology and neurodegeneration in human and model systems. Equally, the collection welcomes translational research that connects these molecular insights with clinical assessment, early intervention, and the lived experiences of individuals and families.

From mechanistic molecular discovery to clinical application, this collection aims to provide a comprehensive and integrative resource for researchers, clinicians, and allied health professionals and foster collaborative efforts to improve diagnosis, management, and quality of life for those affected by FMR1 premutation–associated disorders and fragile X syndrome (FXS).

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: FMR1 premutation, molecular neuropathology, RNA toxicity, neurodegeneration biomarkers, synaptic dysfunction, translational neuroscience, Fragile X, FXPOI, FXAND

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.