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Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies

Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosom...

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Autores principales: López-Hernández, Luz Berenice, Gómez-Díaz, Benjamín, Luna-Angulo, Alexandra Berenice, Anaya-Segura, Mónica, Bunyan, David John, Zúñiga-Guzman, Carolina, Escobar-Cedillo, Rosa Elena, Roque-Ramírez, Bladimir, Ruano-Calderón, Luis Angel, Rangel-Villalobos, Héctor, López-Hernández, Julia Angélica, Estrada-Mena, Francisco Javier, García, Silvia, Coral-Vázquez, Ramón Mauricio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394478/
https://www.ncbi.nlm.nih.gov/pubmed/25761239
http://dx.doi.org/10.3390/ijms16035334
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author López-Hernández, Luz Berenice
Gómez-Díaz, Benjamín
Luna-Angulo, Alexandra Berenice
Anaya-Segura, Mónica
Bunyan, David John
Zúñiga-Guzman, Carolina
Escobar-Cedillo, Rosa Elena
Roque-Ramírez, Bladimir
Ruano-Calderón, Luis Angel
Rangel-Villalobos, Héctor
López-Hernández, Julia Angélica
Estrada-Mena, Francisco Javier
García, Silvia
Coral-Vázquez, Ramón Mauricio
author_facet López-Hernández, Luz Berenice
Gómez-Díaz, Benjamín
Luna-Angulo, Alexandra Berenice
Anaya-Segura, Mónica
Bunyan, David John
Zúñiga-Guzman, Carolina
Escobar-Cedillo, Rosa Elena
Roque-Ramírez, Bladimir
Ruano-Calderón, Luis Angel
Rangel-Villalobos, Héctor
López-Hernández, Julia Angélica
Estrada-Mena, Francisco Javier
García, Silvia
Coral-Vázquez, Ramón Mauricio
author_sort López-Hernández, Luz Berenice
collection PubMed
description Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162) with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001). To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations.
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spelling pubmed-43944782015-05-21 Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies López-Hernández, Luz Berenice Gómez-Díaz, Benjamín Luna-Angulo, Alexandra Berenice Anaya-Segura, Mónica Bunyan, David John Zúñiga-Guzman, Carolina Escobar-Cedillo, Rosa Elena Roque-Ramírez, Bladimir Ruano-Calderón, Luis Angel Rangel-Villalobos, Héctor López-Hernández, Julia Angélica Estrada-Mena, Francisco Javier García, Silvia Coral-Vázquez, Ramón Mauricio Int J Mol Sci Article Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162) with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001). To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations. MDPI 2015-03-09 /pmc/articles/PMC4394478/ /pubmed/25761239 http://dx.doi.org/10.3390/ijms16035334 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
López-Hernández, Luz Berenice
Gómez-Díaz, Benjamín
Luna-Angulo, Alexandra Berenice
Anaya-Segura, Mónica
Bunyan, David John
Zúñiga-Guzman, Carolina
Escobar-Cedillo, Rosa Elena
Roque-Ramírez, Bladimir
Ruano-Calderón, Luis Angel
Rangel-Villalobos, Héctor
López-Hernández, Julia Angélica
Estrada-Mena, Francisco Javier
García, Silvia
Coral-Vázquez, Ramón Mauricio
Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies
title Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies
title_full Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies
title_fullStr Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies
title_full_unstemmed Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies
title_short Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies
title_sort comparison of mutation profiles in the duchenne muscular dystrophy gene among populations: implications for potential molecular therapies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394478/
https://www.ncbi.nlm.nih.gov/pubmed/25761239
http://dx.doi.org/10.3390/ijms16035334
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