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Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation
The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5’ untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529056/ https://www.ncbi.nlm.nih.gov/pubmed/37759552 http://dx.doi.org/10.3390/cells12182330 |
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author | Tassone, Flora Protic, Dragana Allen, Emily Graves Archibald, Alison D. Baud, Anna Brown, Ted W. Budimirovic, Dejan B. Cohen, Jonathan Dufour, Brett Eiges, Rachel Elvassore, Nicola Gabis, Lidia V. Grudzien, Samantha J. Hall, Deborah A. Hessl, David Hogan, Abigail Hunter, Jessica Ezzell Jin, Peng Jiraanont, Poonnada Klusek, Jessica Kooy, R. Frank Kraan, Claudine M. Laterza, Cecilia Lee, Andrea Lipworth, Karen Losh, Molly Loesch, Danuta Lozano, Reymundo Mailick, Marsha R. Manolopoulos, Apostolos Martinez-Cerdeno, Veronica McLennan, Yingratana Miller, Robert M. Montanaro, Federica Alice Maria Mosconi, Matthew W. Potter, Sarah Nelson Raspa, Melissa Rivera, Susan M. Shelly, Katharine Todd, Peter K. Tutak, Katarzyna Wang, Jun Yi Wheeler, Anne Winarni, Tri Indah Zafarullah, Marwa Hagerman, Randi J. |
author_facet | Tassone, Flora Protic, Dragana Allen, Emily Graves Archibald, Alison D. Baud, Anna Brown, Ted W. Budimirovic, Dejan B. Cohen, Jonathan Dufour, Brett Eiges, Rachel Elvassore, Nicola Gabis, Lidia V. Grudzien, Samantha J. Hall, Deborah A. Hessl, David Hogan, Abigail Hunter, Jessica Ezzell Jin, Peng Jiraanont, Poonnada Klusek, Jessica Kooy, R. Frank Kraan, Claudine M. Laterza, Cecilia Lee, Andrea Lipworth, Karen Losh, Molly Loesch, Danuta Lozano, Reymundo Mailick, Marsha R. Manolopoulos, Apostolos Martinez-Cerdeno, Veronica McLennan, Yingratana Miller, Robert M. Montanaro, Federica Alice Maria Mosconi, Matthew W. Potter, Sarah Nelson Raspa, Melissa Rivera, Susan M. Shelly, Katharine Todd, Peter K. Tutak, Katarzyna Wang, Jun Yi Wheeler, Anne Winarni, Tri Indah Zafarullah, Marwa Hagerman, Randi J. |
author_sort | Tassone, Flora |
collection | PubMed |
description | The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5’ untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023. |
format | Online Article Text |
id | pubmed-10529056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105290562023-09-28 Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation Tassone, Flora Protic, Dragana Allen, Emily Graves Archibald, Alison D. Baud, Anna Brown, Ted W. Budimirovic, Dejan B. Cohen, Jonathan Dufour, Brett Eiges, Rachel Elvassore, Nicola Gabis, Lidia V. Grudzien, Samantha J. Hall, Deborah A. Hessl, David Hogan, Abigail Hunter, Jessica Ezzell Jin, Peng Jiraanont, Poonnada Klusek, Jessica Kooy, R. Frank Kraan, Claudine M. Laterza, Cecilia Lee, Andrea Lipworth, Karen Losh, Molly Loesch, Danuta Lozano, Reymundo Mailick, Marsha R. Manolopoulos, Apostolos Martinez-Cerdeno, Veronica McLennan, Yingratana Miller, Robert M. Montanaro, Federica Alice Maria Mosconi, Matthew W. Potter, Sarah Nelson Raspa, Melissa Rivera, Susan M. Shelly, Katharine Todd, Peter K. Tutak, Katarzyna Wang, Jun Yi Wheeler, Anne Winarni, Tri Indah Zafarullah, Marwa Hagerman, Randi J. Cells Review The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5’ untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023. MDPI 2023-09-21 /pmc/articles/PMC10529056/ /pubmed/37759552 http://dx.doi.org/10.3390/cells12182330 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Tassone, Flora Protic, Dragana Allen, Emily Graves Archibald, Alison D. Baud, Anna Brown, Ted W. Budimirovic, Dejan B. Cohen, Jonathan Dufour, Brett Eiges, Rachel Elvassore, Nicola Gabis, Lidia V. Grudzien, Samantha J. Hall, Deborah A. Hessl, David Hogan, Abigail Hunter, Jessica Ezzell Jin, Peng Jiraanont, Poonnada Klusek, Jessica Kooy, R. Frank Kraan, Claudine M. Laterza, Cecilia Lee, Andrea Lipworth, Karen Losh, Molly Loesch, Danuta Lozano, Reymundo Mailick, Marsha R. Manolopoulos, Apostolos Martinez-Cerdeno, Veronica McLennan, Yingratana Miller, Robert M. Montanaro, Federica Alice Maria Mosconi, Matthew W. Potter, Sarah Nelson Raspa, Melissa Rivera, Susan M. Shelly, Katharine Todd, Peter K. Tutak, Katarzyna Wang, Jun Yi Wheeler, Anne Winarni, Tri Indah Zafarullah, Marwa Hagerman, Randi J. Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation |
title | Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation |
title_full | Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation |
title_fullStr | Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation |
title_full_unstemmed | Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation |
title_short | Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation |
title_sort | insight and recommendations for fragile x-premutation-associated conditions from the fifth international conference on fmr1 premutation |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529056/ https://www.ncbi.nlm.nih.gov/pubmed/37759552 http://dx.doi.org/10.3390/cells12182330 |
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