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Molecular Advances Leading to Treatment Implications for Fragile X Premutation Carriers

Fragile X syndrome (FXS) is the most common single gene cause of intellectual disability and it is characterized by a CGG expansion of more than 200 repeats in the FMR1 gene, leading to methylation of the promoter and gene silencing. The fragile X premutation, characterized by a 55 to 200 CGG repeat...

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Autores principales: Polussa, Jonathan, Schneider, Andrea, Hagerman, Randi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245015/
https://www.ncbi.nlm.nih.gov/pubmed/25436181
http://dx.doi.org/10.4172/2168-975X.1000119
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author Polussa, Jonathan
Schneider, Andrea
Hagerman, Randi
author_facet Polussa, Jonathan
Schneider, Andrea
Hagerman, Randi
author_sort Polussa, Jonathan
collection PubMed
description Fragile X syndrome (FXS) is the most common single gene cause of intellectual disability and it is characterized by a CGG expansion of more than 200 repeats in the FMR1 gene, leading to methylation of the promoter and gene silencing. The fragile X premutation, characterized by a 55 to 200 CGG repeat expansion, causes health problems and developmental difficulties in some, but not all, carriers. The premutation causes primary ovarian insufficiency in approximately 20% of females, psychiatric problems (including depression and/or anxiety) in approximately 50% of carriers and a neurodegenerative disorder, the fragile X-associated tremor ataxia syndrome (FXTAS), in approximately 40% of males and 16% of females later in life. Recent clinical studies in premutation carriers have expanded the health problems that may be seen. Advances in the molecular pathogenesis of the premutation have shown significant mitochondrial dysfunction and oxidative stress in neurons which may be amenable to treatment. Here we review the clinical problems of carriers and treatment recommendations.
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spelling pubmed-42450152014-11-26 Molecular Advances Leading to Treatment Implications for Fragile X Premutation Carriers Polussa, Jonathan Schneider, Andrea Hagerman, Randi Brain Disord Ther Article Fragile X syndrome (FXS) is the most common single gene cause of intellectual disability and it is characterized by a CGG expansion of more than 200 repeats in the FMR1 gene, leading to methylation of the promoter and gene silencing. The fragile X premutation, characterized by a 55 to 200 CGG repeat expansion, causes health problems and developmental difficulties in some, but not all, carriers. The premutation causes primary ovarian insufficiency in approximately 20% of females, psychiatric problems (including depression and/or anxiety) in approximately 50% of carriers and a neurodegenerative disorder, the fragile X-associated tremor ataxia syndrome (FXTAS), in approximately 40% of males and 16% of females later in life. Recent clinical studies in premutation carriers have expanded the health problems that may be seen. Advances in the molecular pathogenesis of the premutation have shown significant mitochondrial dysfunction and oxidative stress in neurons which may be amenable to treatment. Here we review the clinical problems of carriers and treatment recommendations. 2014-04-05 2014 /pmc/articles/PMC4245015/ /pubmed/25436181 http://dx.doi.org/10.4172/2168-975X.1000119 Text en Copyright: © 2014 Randi Hagerman, et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Article
Polussa, Jonathan
Schneider, Andrea
Hagerman, Randi
Molecular Advances Leading to Treatment Implications for Fragile X Premutation Carriers
title Molecular Advances Leading to Treatment Implications for Fragile X Premutation Carriers
title_full Molecular Advances Leading to Treatment Implications for Fragile X Premutation Carriers
title_fullStr Molecular Advances Leading to Treatment Implications for Fragile X Premutation Carriers
title_full_unstemmed Molecular Advances Leading to Treatment Implications for Fragile X Premutation Carriers
title_short Molecular Advances Leading to Treatment Implications for Fragile X Premutation Carriers
title_sort molecular advances leading to treatment implications for fragile x premutation carriers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245015/
https://www.ncbi.nlm.nih.gov/pubmed/25436181
http://dx.doi.org/10.4172/2168-975X.1000119
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