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Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes
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-a...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395059/ https://www.ncbi.nlm.nih.gov/pubmed/34445074 http://dx.doi.org/10.3390/ijms22168368 |
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author | Valor, Luis M. Morales, Jorge C. Hervás-Corpión, Irati Marín, Rosario |
author_facet | Valor, Luis M. Morales, Jorge C. Hervás-Corpión, Irati Marín, Rosario |
author_sort | Valor, Luis M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8395059 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83950592021-08-28 Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes Valor, Luis M. Morales, Jorge C. Hervás-Corpión, Irati Marín, Rosario Int J Mol Sci Review 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. MDPI 2021-08-04 /pmc/articles/PMC8395059/ /pubmed/34445074 http://dx.doi.org/10.3390/ijms22168368 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Valor, Luis M. Morales, Jorge C. Hervás-Corpión, Irati Marín, Rosario Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes |
title | Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes |
title_full | Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes |
title_fullStr | Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes |
title_full_unstemmed | Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes |
title_short | Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes |
title_sort | molecular pathogenesis and peripheral monitoring of adult fragile x-associated syndromes |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395059/ https://www.ncbi.nlm.nih.gov/pubmed/34445074 http://dx.doi.org/10.3390/ijms22168368 |
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