Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes
| Autor: | Valor, Luis M., Morales, Jorge C., Hervás-Corpión, Irati, Marín, Rosario |
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| Přispěvatelé: | [Valor,LM] Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain. [Valor,LM] Laboratorio de Apoyo a la Investigación, Hospital General Universitario de Alicante, Alicante, Spain. [Valor,LM, Morales,JC, Hervás-Corpión,I, Marín,R] Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain. [Valor,LM, Hervás-Corpión,I] Unidad de Investigación, Hospital Universitario Puerta del Mar, Cádiz, Spain. [Marín,R] Unidad de Genética, Hospital Universitario Puerta del Mar, Cádiz, Spain., L.M.V. is supported by the Programa Estatal de Generación de Conocimiento, financed by the Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional 2014-2020 (Grants PI16/00722 and PI19/00125). L.M.V. is the recipient of a Miguel Servet I contract (CP15/00180) followed by a Miguel Servet II contract (CPII20/00025), and J.C.M. is the recipient of a Río Hortega contract (CM18/00043), all financed by the Instituto de Salud Carlos III and Fondo Social Europeo 2014-2020, Programa Estatal de Promoción del Talento y su empleabilidad en I+D+i. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation [Medical Subject Headings]
FXAND Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] GABA Fragile X Mental Retardation Protein Phenomena and Processes::Genetic Phenomena::Genetic Processes::Mutagenesis::DNA Repeat Expansion::Trinucleotide Repeat Expansion [Medical Subject Headings] Diseases::Female Urogenital Diseases and Pregnancy Complications::Female Urogenital Diseases::Genital Diseases Female::Adnexal Diseases::Ovarian Diseases::Primary Ovarian Insufficiency [Medical Subject Headings] Organisms::Eukaryota::Animals [Medical Subject Headings] Persons::Persons::Age Groups::Adult [Medical Subject Headings] FMR1 FXPOI Mitocondrias miRNA Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Mitochondria [Medical Subject Headings] MicroARNs Diseases::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual Disability::Mental Retardation X-Linked::Fragile X Syndrome [Medical Subject Headings] Sangre Biomarker Telomere Mitochondria Transcripción genética Blood Biomarcadores Check Tags::Female [Medical Subject Headings] Diseases::Nervous System Diseases::Neurologic Manifestations::Dyskinesias::Ataxia [Medical Subject Headings] Premutation FXTAS Diseases::Nervous System Diseases::Neurologic Manifestations::Dyskinesias::Tremor [Medical Subject Headings] FMRP Endocrine Transcription Telómero |
| Popis: | 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. Yes |
| Databáze: | OpenAIRE |
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