Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes.
Por:
Valor LM, Morales JC, Hervás-Corpión I and Marín R
Publicada:
4 ago 2021
Ahead of Print:
4 ago 2021
Resumen:
Abnormal trinucleotide expansions cause rare disorders that compromise quality of life and, in some cases, lifespan. In particular, the expansions of the CGG-repeats stretch at the 5'-UTR of the Fragile X Mental Retardation 1 (FMR1) gene have pleiotropic effects that lead to a variety of Fragile X-associated syndromes: the neurodevelopmental Fragile X syndrome (FXS) in children, the late-onset neurodegenerative disorder Fragile X-associated tremor-ataxia syndrome (FXTAS) that mainly affects adult men, the Fragile X-associated primary ovarian insufficiency (FXPOI) in adult women, and a variety of psychiatric and affective disorders that are under the term of Fragile X-associated neuropsychiatric disorders (FXAND). In this review, we will describe the pathological mechanisms of the adult "gain-of-function" syndromes that are mainly caused by the toxic actions of CGG RNA and FMRpolyG peptide. There have been intensive attempts to identify reliable peripheral biomarkers to assess disease progression and onset of specific pathological traits. Mitochondrial dysfunction, altered miRNA expression, endocrine system failure, and impairment of the GABAergic transmission are some of the affectations that are susceptible to be tracked using peripheral blood for monitoring of the motor, cognitive, psychiatric and reproductive impairment of the CGG-expansion carriers. We provided some illustrative examples from our own cohort. Understanding the association between molecular pathogenesis and biomarkers dynamics will improve effective prognosis and clinical management of CGG-expansion carriers.
Filiaciones:
:
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), 03010 Alicante, Spain
Laboratorio de Apoyo a la Investigación, Hospital General Universitario de Alicante, Av. Pintor Baeza 12, 03010 Alicante, Spain
Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain
Unidad de Investigación, Hospital Universitario Puerta del Mar, Av. Ana de Viya 21, 11009 Cádiz, Spain
Morales JC:
Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain
Unidad de Investigación, Hospital Universitario Puerta del Mar, Av. Ana de Viya 21, 11009 Cádiz, Spain
Hervás-Corpión I:
Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain
Unidad de Investigación, Hospital Universitario Puerta del Mar, Av. Ana de Viya 21, 11009 Cádiz, Spain
Marín R:
Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cádiz, Spain
Unidad de Genética, Hospital Universitario Puerta del Mar, Av. Ana de Viya 21, 11009 Cádiz, Spain
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