Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes.
DMD nonsense and frameshift mutations lead to severe Duchenne muscular dystrophy while in-frame mutations lead to milder Becker muscular dystrophy. Exceptions are found in 10% of cases and the production of alternatively spliced transcripts is considered a key modifier of disease severity. Several e...
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doaj-01f25a8e27ed4e2ab08cfcd4aa96e7342020-11-25T00:53:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5991610.1371/journal.pone.0059916Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes.Jonàs Juan-MateuLidia González-QueredaMaria José RodríguezEdgard VerduraKira LázaroCristina JouAndrés NascimentoCecilia Jiménez-MallebreraJaume ColomerSoledad MongesFabiana LubienieckiMaria Eugenia FoncubertaSamuel Ignacio Pascual-PascualJesús MolanoMontserrat BaigetPia GallanoDMD nonsense and frameshift mutations lead to severe Duchenne muscular dystrophy while in-frame mutations lead to milder Becker muscular dystrophy. Exceptions are found in 10% of cases and the production of alternatively spliced transcripts is considered a key modifier of disease severity. Several exonic mutations have been shown to induce exon-skipping, while splice site mutations result in exon-skipping or activation of cryptic splice sites. However, factors determining the splicing pathway are still unclear. Point mutations provide valuable information regarding the regulation of pre-mRNA splicing and elements defining exon identity in the DMD gene. Here we provide a comprehensive analysis of 98 point mutations related to clinical phenotype and their effect on muscle mRNA and dystrophin expression. Aberrant splicing was found in 27 mutations due to alteration of splice sites or splicing regulatory elements. Bioinformatics analysis was performed to test the ability of the available algorithms to predict consequences on mRNA and to investigate the major factors that determine the splicing pathway in mutations affecting splicing signals. Our findings suggest that the splicing pathway is highly dependent on the interplay between splice site strength and density of regulatory elements.http://europepmc.org/articles/PMC3607557?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jonàs Juan-Mateu Lidia González-Quereda Maria José Rodríguez Edgard Verdura Kira Lázaro Cristina Jou Andrés Nascimento Cecilia Jiménez-Mallebrera Jaume Colomer Soledad Monges Fabiana Lubieniecki Maria Eugenia Foncuberta Samuel Ignacio Pascual-Pascual Jesús Molano Montserrat Baiget Pia Gallano |
spellingShingle |
Jonàs Juan-Mateu Lidia González-Quereda Maria José Rodríguez Edgard Verdura Kira Lázaro Cristina Jou Andrés Nascimento Cecilia Jiménez-Mallebrera Jaume Colomer Soledad Monges Fabiana Lubieniecki Maria Eugenia Foncuberta Samuel Ignacio Pascual-Pascual Jesús Molano Montserrat Baiget Pia Gallano Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes. PLoS ONE |
author_facet |
Jonàs Juan-Mateu Lidia González-Quereda Maria José Rodríguez Edgard Verdura Kira Lázaro Cristina Jou Andrés Nascimento Cecilia Jiménez-Mallebrera Jaume Colomer Soledad Monges Fabiana Lubieniecki Maria Eugenia Foncuberta Samuel Ignacio Pascual-Pascual Jesús Molano Montserrat Baiget Pia Gallano |
author_sort |
Jonàs Juan-Mateu |
title |
Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes. |
title_short |
Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes. |
title_full |
Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes. |
title_fullStr |
Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes. |
title_full_unstemmed |
Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes. |
title_sort |
interplay between dmd point mutations and splicing signals in dystrophinopathy phenotypes. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
DMD nonsense and frameshift mutations lead to severe Duchenne muscular dystrophy while in-frame mutations lead to milder Becker muscular dystrophy. Exceptions are found in 10% of cases and the production of alternatively spliced transcripts is considered a key modifier of disease severity. Several exonic mutations have been shown to induce exon-skipping, while splice site mutations result in exon-skipping or activation of cryptic splice sites. However, factors determining the splicing pathway are still unclear. Point mutations provide valuable information regarding the regulation of pre-mRNA splicing and elements defining exon identity in the DMD gene. Here we provide a comprehensive analysis of 98 point mutations related to clinical phenotype and their effect on muscle mRNA and dystrophin expression. Aberrant splicing was found in 27 mutations due to alteration of splice sites or splicing regulatory elements. Bioinformatics analysis was performed to test the ability of the available algorithms to predict consequences on mRNA and to investigate the major factors that determine the splicing pathway in mutations affecting splicing signals. Our findings suggest that the splicing pathway is highly dependent on the interplay between splice site strength and density of regulatory elements. |
url |
http://europepmc.org/articles/PMC3607557?pdf=render |
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