Publication:
Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes

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2021-08-04

Authors

Valor, Luis M.
Morales, Jorge C.
Hervás-Corpión, Irati
Marín, Rosario

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MDPI
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Abstract

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.

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Medical Subject Headings::Persons::Persons::Age Groups::Adult
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Dyskinesias::Ataxia
Medical Subject Headings::Check Tags::Female
Fragile X Mental Retardation Protein
Medical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual Disability::Mental Retardation, X-Linked::Fragile X Syndrome
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Mitochondria
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::Diseases::Nervous System Diseases::Neurologic Manifestations::Dyskinesias::Tremor
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Mutagenesis::DNA Repeat Expansion::Trinucleotide Repeat Expansion

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Keywords

FXTAS, FXPOI, FXAND, Premutation, Blood, Biomarker, FMR1, FMRP, Endocrine, Mitochondria, miRNA, Transcription, GABA, Telomere, Sangre, Biomarcadores, Mitocondrias, MicroARNs, Transcripción genética, Telómero

Citation

Valor LM, Morales JC, Hervás-Corpión I, Marín R. Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes. Int J Mol Sci. 2021 Aug 4;22(16):8368