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Analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism

Cerebral palsy (CP) is the most common motor disability of childhood. It is characterised by permanent, non-progressive but not unchanging problems with movement, posture and motor function, with a highly heterogeneous clinical spectrum and frequent neurodevelopmental comorbidities. The aetiology of...

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Autores principales: van Eyk, Clare L., Corbett, Mark A., Gardner, Alison, van Bon, Bregje W., Broadbent, Jessica L., Harper, Kelly, MacLennan, Alastair H., Gecz, Jozef
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911435/
https://www.ncbi.nlm.nih.gov/pubmed/29681622
http://dx.doi.org/10.1038/s41398-018-0136-4
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author van Eyk, Clare L.
Corbett, Mark A.
Gardner, Alison
van Bon, Bregje W.
Broadbent, Jessica L.
Harper, Kelly
MacLennan, Alastair H.
Gecz, Jozef
author_facet van Eyk, Clare L.
Corbett, Mark A.
Gardner, Alison
van Bon, Bregje W.
Broadbent, Jessica L.
Harper, Kelly
MacLennan, Alastair H.
Gecz, Jozef
author_sort van Eyk, Clare L.
collection PubMed
description Cerebral palsy (CP) is the most common motor disability of childhood. It is characterised by permanent, non-progressive but not unchanging problems with movement, posture and motor function, with a highly heterogeneous clinical spectrum and frequent neurodevelopmental comorbidities. The aetiology of CP is poorly understood, despite recent reports of a genetic contribution in some cases. Here we demonstrate transcriptional dysregulation of trophic signalling pathways in patient-derived cell lines from an unselected cohort of 182 CP-affected individuals using both differential expression analysis and weighted gene co-expression network analysis (WGCNA). We also show that genes differentially expressed in CP, as well as network modules significantly correlated with CP status, are enriched for genes associated with ASD. Combining transcriptome and whole exome sequencing (WES) data for this CP cohort likely resolves an additional 5% of cases separated to the 14% we have previously reported as resolved by WES. Collectively, these results support a convergent molecular abnormality in CP and ASD.
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spelling pubmed-59114352018-04-23 Analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism van Eyk, Clare L. Corbett, Mark A. Gardner, Alison van Bon, Bregje W. Broadbent, Jessica L. Harper, Kelly MacLennan, Alastair H. Gecz, Jozef Transl Psychiatry Article Cerebral palsy (CP) is the most common motor disability of childhood. It is characterised by permanent, non-progressive but not unchanging problems with movement, posture and motor function, with a highly heterogeneous clinical spectrum and frequent neurodevelopmental comorbidities. The aetiology of CP is poorly understood, despite recent reports of a genetic contribution in some cases. Here we demonstrate transcriptional dysregulation of trophic signalling pathways in patient-derived cell lines from an unselected cohort of 182 CP-affected individuals using both differential expression analysis and weighted gene co-expression network analysis (WGCNA). We also show that genes differentially expressed in CP, as well as network modules significantly correlated with CP status, are enriched for genes associated with ASD. Combining transcriptome and whole exome sequencing (WES) data for this CP cohort likely resolves an additional 5% of cases separated to the 14% we have previously reported as resolved by WES. Collectively, these results support a convergent molecular abnormality in CP and ASD. Nature Publishing Group UK 2018-04-23 /pmc/articles/PMC5911435/ /pubmed/29681622 http://dx.doi.org/10.1038/s41398-018-0136-4 Text en © The Author(s) 2018 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
van Eyk, Clare L.
Corbett, Mark A.
Gardner, Alison
van Bon, Bregje W.
Broadbent, Jessica L.
Harper, Kelly
MacLennan, Alastair H.
Gecz, Jozef
Analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism
title Analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism
title_full Analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism
title_fullStr Analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism
title_full_unstemmed Analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism
title_short Analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism
title_sort analysis of 182 cerebral palsy transcriptomes points to dysregulation of trophic signalling pathways and overlap with autism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911435/
https://www.ncbi.nlm.nih.gov/pubmed/29681622
http://dx.doi.org/10.1038/s41398-018-0136-4
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