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: | ; ; ; |
|---|---|
| Tipo de documento: | Artículo |
| Estado: | Published version |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| Repositorio: | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| OAI Identifier: | oai:isabial.fundanetsuite.com:p7357 |
| Acceso en línea: | https://isabial.portalinvestigacion.com/publicaciones7357 https://doi.org/10.3390/ijms22168368 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | FMR1 FMRP FXAND FXPOI FXTAS GABA biomarker blood endocrine miRNA mitochondria premutation telomere transcription |
| _version_ | 1878738722587934720 |
|---|---|
| author | Valor LM |
| author2 | Morales JC Hervás-Corpión I Marín R |
| author2_role | author author author |
| author_browse | Hervás-Corpión I Marín R Morales JC Valor LM |
| author_facet | Valor LM Morales JC Hervás-Corpión I Marín R |
| author_role | author |
| collection | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_b3edfb69ae8ece4a9113e2f655b39274 |
| institution | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| instname_str | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:isabial.fundanetsuite.com:p7357 |
| publishDate | 2021 |
| publishDateSort | 2021 |
| publisher | MDPI |
| publisherStr | MDPI |
| reponame_str | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| spelling | Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes. Valor LM Morales JC Hervás-Corpión I Marín R FMR1 FMRP FXAND FXPOI FXTAS GABA biomarker blood endocrine miRNA mitochondria premutation telomere transcription 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 https://isabial.portalinvestigacion.com/publicaciones7357 https://doi.org/10.3390/ijms22168368 |
| spellingShingle | Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes. Valor LM FMR1 FMRP FXAND FXPOI FXTAS GABA biomarker blood endocrine miRNA mitochondria premutation telomere transcription |
| status_str | publishedVersion |
| 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 | FMR1 FMRP FXAND FXPOI FXTAS GABA biomarker blood endocrine miRNA mitochondria premutation telomere transcription |
| topic_facet | FMR1 FMRP FXAND FXPOI FXTAS GABA biomarker blood endocrine miRNA mitochondria premutation telomere transcription |
| url | https://isabial.portalinvestigacion.com/publicaciones7357 https://doi.org/10.3390/ijms22168368 |