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Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions
Rett syndrome (RTT) and Fragile X syndrome (FXS) are two monogenetic neurodevelopmental disorders with complex clinical presentations. RTT is caused by mutations in the Methyl-CpG binding protein 2 gene (MECP2) altering the function of its protein product MeCP2. MeCP2 modulates gene expression by bi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640214/ https://www.ncbi.nlm.nih.gov/pubmed/34867203 http://dx.doi.org/10.3389/fncel.2021.764761 |
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author | Bach, Snow Shovlin, Stephen Moriarty, Michael Bardoni, Barbara Tropea, Daniela |
author_facet | Bach, Snow Shovlin, Stephen Moriarty, Michael Bardoni, Barbara Tropea, Daniela |
author_sort | Bach, Snow |
collection | PubMed |
description | Rett syndrome (RTT) and Fragile X syndrome (FXS) are two monogenetic neurodevelopmental disorders with complex clinical presentations. RTT is caused by mutations in the Methyl-CpG binding protein 2 gene (MECP2) altering the function of its protein product MeCP2. MeCP2 modulates gene expression by binding methylated CpG dinucleotides, and by interacting with transcription factors. FXS is caused by the silencing of the FMR1 gene encoding the Fragile X Mental Retardation Protein (FMRP), a RNA binding protein involved in multiple steps of RNA metabolism, and modulating the translation of thousands of proteins including a large set of synaptic proteins. Despite differences in genetic etiology, there are overlapping features in RTT and FXS, possibly due to interactions between MeCP2 and FMRP, and to the regulation of pathways resulting in dysregulation of common molecular signaling. Furthermore, basic physiological mechanisms are regulated by these proteins and might concur to the pathophysiology of both syndromes. Considering that RTT and FXS are disorders affecting brain development, and that most of the common targets of MeCP2 and FMRP are involved in brain activity, we discuss the mechanisms of synaptic function and plasticity altered in RTT and FXS, and we consider the similarities and the differences between these two disorders. |
format | Online Article Text |
id | pubmed-8640214 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86402142021-12-04 Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions Bach, Snow Shovlin, Stephen Moriarty, Michael Bardoni, Barbara Tropea, Daniela Front Cell Neurosci Neuroscience Rett syndrome (RTT) and Fragile X syndrome (FXS) are two monogenetic neurodevelopmental disorders with complex clinical presentations. RTT is caused by mutations in the Methyl-CpG binding protein 2 gene (MECP2) altering the function of its protein product MeCP2. MeCP2 modulates gene expression by binding methylated CpG dinucleotides, and by interacting with transcription factors. FXS is caused by the silencing of the FMR1 gene encoding the Fragile X Mental Retardation Protein (FMRP), a RNA binding protein involved in multiple steps of RNA metabolism, and modulating the translation of thousands of proteins including a large set of synaptic proteins. Despite differences in genetic etiology, there are overlapping features in RTT and FXS, possibly due to interactions between MeCP2 and FMRP, and to the regulation of pathways resulting in dysregulation of common molecular signaling. Furthermore, basic physiological mechanisms are regulated by these proteins and might concur to the pathophysiology of both syndromes. Considering that RTT and FXS are disorders affecting brain development, and that most of the common targets of MeCP2 and FMRP are involved in brain activity, we discuss the mechanisms of synaptic function and plasticity altered in RTT and FXS, and we consider the similarities and the differences between these two disorders. Frontiers Media S.A. 2021-11-19 /pmc/articles/PMC8640214/ /pubmed/34867203 http://dx.doi.org/10.3389/fncel.2021.764761 Text en Copyright © 2021 Bach, Shovlin, Moriarty, Bardoni and Tropea. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Bach, Snow Shovlin, Stephen Moriarty, Michael Bardoni, Barbara Tropea, Daniela Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions |
title | Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions |
title_full | Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions |
title_fullStr | Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions |
title_full_unstemmed | Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions |
title_short | Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions |
title_sort | rett syndrome and fragile x syndrome: different etiology with common molecular dysfunctions |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640214/ https://www.ncbi.nlm.nih.gov/pubmed/34867203 http://dx.doi.org/10.3389/fncel.2021.764761 |
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