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Increasing our Understanding of Human Cognition Through the Study of Fragile X Syndrome

Fragile X Syndrome (FXS) is considered the most common form of inherited intellectual disability. It is caused by reductions in the expression level or function of a single protein, the Fragile X Mental Retardation Protein (FMRP), a translational regulator which binds to approximately 4% of brain me...

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Autores principales: Denise, Cook, Erin, Nuro, Keith, K. Murai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216185/
https://www.ncbi.nlm.nih.gov/pubmed/23723176
http://dx.doi.org/10.1002/dneu.22096
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author Denise, Cook
Erin, Nuro
Keith, K. Murai
author_facet Denise, Cook
Erin, Nuro
Keith, K. Murai
author_sort Denise, Cook
collection PubMed
description Fragile X Syndrome (FXS) is considered the most common form of inherited intellectual disability. It is caused by reductions in the expression level or function of a single protein, the Fragile X Mental Retardation Protein (FMRP), a translational regulator which binds to approximately 4% of brain messenger RNAs. Accumulating evidence suggests that FXS is a complex disorder of cognition, involving interactions between genetic and environmental influences, leading to difficulties in acquiring key life skills including motor skills, language, and proper social behaviors. Since many FXS patients also present with one or more features of autism spectrum disorders (ASDs), insights gained from studying the monogenic basis of FXS could pave the way to a greater understanding of underlying features of multigenic ASDs. Here we present an overview of the FXS and FMRP field with the goal of demonstrating how loss of a single protein involved in translational control affects multiple stages of brain development and leads to debilitating consequences on human cognition. We also focus on studies which have rescued or improved FXS symptoms in mice using genetic or therapeutic approaches to reduce protein expression. We end with a brief description of how deficits in translational control are implicated in FXS and certain cases of ASDs, with many recent studies demonstrating that ASDs are likely caused by increases or decreases in the levels of certain key synaptic proteins. The study of FXS and its underlying single genetic cause offers an invaluable opportunity to study how a single gene influences brain development and behavior. © 2013 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 74: 147–177, 2014
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spelling pubmed-42161852014-12-15 Increasing our Understanding of Human Cognition Through the Study of Fragile X Syndrome Denise, Cook Erin, Nuro Keith, K. Murai Dev Neurobiol Review Articles Fragile X Syndrome (FXS) is considered the most common form of inherited intellectual disability. It is caused by reductions in the expression level or function of a single protein, the Fragile X Mental Retardation Protein (FMRP), a translational regulator which binds to approximately 4% of brain messenger RNAs. Accumulating evidence suggests that FXS is a complex disorder of cognition, involving interactions between genetic and environmental influences, leading to difficulties in acquiring key life skills including motor skills, language, and proper social behaviors. Since many FXS patients also present with one or more features of autism spectrum disorders (ASDs), insights gained from studying the monogenic basis of FXS could pave the way to a greater understanding of underlying features of multigenic ASDs. Here we present an overview of the FXS and FMRP field with the goal of demonstrating how loss of a single protein involved in translational control affects multiple stages of brain development and leads to debilitating consequences on human cognition. We also focus on studies which have rescued or improved FXS symptoms in mice using genetic or therapeutic approaches to reduce protein expression. We end with a brief description of how deficits in translational control are implicated in FXS and certain cases of ASDs, with many recent studies demonstrating that ASDs are likely caused by increases or decreases in the levels of certain key synaptic proteins. The study of FXS and its underlying single genetic cause offers an invaluable opportunity to study how a single gene influences brain development and behavior. © 2013 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 74: 147–177, 2014 BlackWell Publishing Ltd 2014-01 2013-05-31 /pmc/articles/PMC4216185/ /pubmed/23723176 http://dx.doi.org/10.1002/dneu.22096 Text en Copyright © 2013 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Review Articles
Denise, Cook
Erin, Nuro
Keith, K. Murai
Increasing our Understanding of Human Cognition Through the Study of Fragile X Syndrome
title Increasing our Understanding of Human Cognition Through the Study of Fragile X Syndrome
title_full Increasing our Understanding of Human Cognition Through the Study of Fragile X Syndrome
title_fullStr Increasing our Understanding of Human Cognition Through the Study of Fragile X Syndrome
title_full_unstemmed Increasing our Understanding of Human Cognition Through the Study of Fragile X Syndrome
title_short Increasing our Understanding of Human Cognition Through the Study of Fragile X Syndrome
title_sort increasing our understanding of human cognition through the study of fragile x syndrome
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216185/
https://www.ncbi.nlm.nih.gov/pubmed/23723176
http://dx.doi.org/10.1002/dneu.22096
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