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Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a muscular dystrophy with high incidence of learning and behavioural problems and is associated with neurodevelopmental disorders. To gain more insights into the role of dystrophin in this cognitive phenotype, we performed a comprehensive analysis of the expressi...

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Autores principales: Doorenweerd, Nathalie, Mahfouz, Ahmed, van Putten, Maaike, Kaliyaperumal, Rajaram, t’ Hoen, Peter A. C., Hendriksen, Jos G. M., Aartsma-Rus, Annemieke M., Verschuuren, Jan J. G. M., Niks, Erik H., Reinders, Marcel J. T., Kan, Hermien E., Lelieveldt, Boudewijn P. F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626779/
https://www.ncbi.nlm.nih.gov/pubmed/28974727
http://dx.doi.org/10.1038/s41598-017-12981-5
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author Doorenweerd, Nathalie
Mahfouz, Ahmed
van Putten, Maaike
Kaliyaperumal, Rajaram
t’ Hoen, Peter A. C.
Hendriksen, Jos G. M.
Aartsma-Rus, Annemieke M.
Verschuuren, Jan J. G. M.
Niks, Erik H.
Reinders, Marcel J. T.
Kan, Hermien E.
Lelieveldt, Boudewijn P. F.
author_facet Doorenweerd, Nathalie
Mahfouz, Ahmed
van Putten, Maaike
Kaliyaperumal, Rajaram
t’ Hoen, Peter A. C.
Hendriksen, Jos G. M.
Aartsma-Rus, Annemieke M.
Verschuuren, Jan J. G. M.
Niks, Erik H.
Reinders, Marcel J. T.
Kan, Hermien E.
Lelieveldt, Boudewijn P. F.
author_sort Doorenweerd, Nathalie
collection PubMed
description Duchenne muscular dystrophy (DMD) is a muscular dystrophy with high incidence of learning and behavioural problems and is associated with neurodevelopmental disorders. To gain more insights into the role of dystrophin in this cognitive phenotype, we performed a comprehensive analysis of the expression patterns of dystrophin isoforms across human brain development, using unique transcriptomic data from Allen Human Brain and BrainSpan atlases. Dystrophin isoforms show large changes in expression through life with pronounced differences between the foetal and adult human brain. The Dp140 isoform was expressed in the cerebral cortex only in foetal life stages, while in the cerebellum it was also expressed postnatally. The Purkinje isoform Dp427p was virtually absent. The expression of dystrophin isoforms was significantly associated with genes implicated in neurodevelopmental disorders, like autism spectrum disorders or attention-deficit hyper-activity disorders, which are known to be associated to DMD. We also identified relevant functional associations of the different isoforms, like an association with axon guidance or neuron differentiation during early development. Our results point to the crucial role of several dystrophin isoforms in the development and function of the human brain.
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spelling pubmed-56267792017-10-12 Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy Doorenweerd, Nathalie Mahfouz, Ahmed van Putten, Maaike Kaliyaperumal, Rajaram t’ Hoen, Peter A. C. Hendriksen, Jos G. M. Aartsma-Rus, Annemieke M. Verschuuren, Jan J. G. M. Niks, Erik H. Reinders, Marcel J. T. Kan, Hermien E. Lelieveldt, Boudewijn P. F. Sci Rep Article Duchenne muscular dystrophy (DMD) is a muscular dystrophy with high incidence of learning and behavioural problems and is associated with neurodevelopmental disorders. To gain more insights into the role of dystrophin in this cognitive phenotype, we performed a comprehensive analysis of the expression patterns of dystrophin isoforms across human brain development, using unique transcriptomic data from Allen Human Brain and BrainSpan atlases. Dystrophin isoforms show large changes in expression through life with pronounced differences between the foetal and adult human brain. The Dp140 isoform was expressed in the cerebral cortex only in foetal life stages, while in the cerebellum it was also expressed postnatally. The Purkinje isoform Dp427p was virtually absent. The expression of dystrophin isoforms was significantly associated with genes implicated in neurodevelopmental disorders, like autism spectrum disorders or attention-deficit hyper-activity disorders, which are known to be associated to DMD. We also identified relevant functional associations of the different isoforms, like an association with axon guidance or neuron differentiation during early development. Our results point to the crucial role of several dystrophin isoforms in the development and function of the human brain. Nature Publishing Group UK 2017-10-03 /pmc/articles/PMC5626779/ /pubmed/28974727 http://dx.doi.org/10.1038/s41598-017-12981-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Doorenweerd, Nathalie
Mahfouz, Ahmed
van Putten, Maaike
Kaliyaperumal, Rajaram
t’ Hoen, Peter A. C.
Hendriksen, Jos G. M.
Aartsma-Rus, Annemieke M.
Verschuuren, Jan J. G. M.
Niks, Erik H.
Reinders, Marcel J. T.
Kan, Hermien E.
Lelieveldt, Boudewijn P. F.
Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy
title Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy
title_full Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy
title_fullStr Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy
title_full_unstemmed Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy
title_short Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy
title_sort timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of duchenne muscular dystrophy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626779/
https://www.ncbi.nlm.nih.gov/pubmed/28974727
http://dx.doi.org/10.1038/s41598-017-12981-5
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