Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Valor, Luis M., Morales, Jorge C., Hervás-Corpión, Irati, Marín, Rosario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1783744086573842432
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
work_keys_str_mv AT valorluism molecularpathogenesisandperipheralmonitoringofadultfragilexassociatedsyndromes
AT moralesjorgec molecularpathogenesisandperipheralmonitoringofadultfragilexassociatedsyndromes
AT hervascorpionirati molecularpathogenesisandperipheralmonitoringofadultfragilexassociatedsyndromes
AT marinrosario molecularpathogenesisandperipheralmonitoringofadultfragilexassociatedsyndromes