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Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development

Autism is a prevailing neurodevelopmental disorder with a large genetic/genomic component. Recently, the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) gene was implicated as a risk factor for autism spectrum disorder (ASD). We identified five DYRK1A variants in ASD pati...

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Autores principales: Dang, T, Duan, W Y, Yu, B, Tong, D L, Cheng, C, Zhang, Y F, Wu, W, Ye, K, Zhang, W X, Wu, M, Wu, B B, An, Y, Qiu, Z L, Wu, B L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822466/
https://www.ncbi.nlm.nih.gov/pubmed/28167836
http://dx.doi.org/10.1038/mp.2016.253
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author Dang, T
Duan, W Y
Yu, B
Tong, D L
Cheng, C
Zhang, Y F
Wu, W
Ye, K
Zhang, W X
Wu, M
Wu, B B
An, Y
Qiu, Z L
Wu, B L
author_facet Dang, T
Duan, W Y
Yu, B
Tong, D L
Cheng, C
Zhang, Y F
Wu, W
Ye, K
Zhang, W X
Wu, M
Wu, B B
An, Y
Qiu, Z L
Wu, B L
author_sort Dang, T
collection PubMed
description Autism is a prevailing neurodevelopmental disorder with a large genetic/genomic component. Recently, the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) gene was implicated as a risk factor for autism spectrum disorder (ASD). We identified five DYRK1A variants in ASD patients and found that the dose of DYRK1A protein has a crucial role in various aspects of postnatal neural development. Dyrk1a loss of function and gain of function led to defects in dendritic growth, dendritic spine development and radial migration during cortical development. Importantly, two autism-associated truncations, R205X and E239X, were shown to be Dyrk1a loss-of-function mutants. Studies of the truncated Dyrk1a mutants may provide new insights into the role of Dyrk1a in brain development, as well as the role of Dyrk1a loss of function in the pathophysiology of autism.
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spelling pubmed-58224662018-02-23 Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development Dang, T Duan, W Y Yu, B Tong, D L Cheng, C Zhang, Y F Wu, W Ye, K Zhang, W X Wu, M Wu, B B An, Y Qiu, Z L Wu, B L Mol Psychiatry Original Article Autism is a prevailing neurodevelopmental disorder with a large genetic/genomic component. Recently, the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) gene was implicated as a risk factor for autism spectrum disorder (ASD). We identified five DYRK1A variants in ASD patients and found that the dose of DYRK1A protein has a crucial role in various aspects of postnatal neural development. Dyrk1a loss of function and gain of function led to defects in dendritic growth, dendritic spine development and radial migration during cortical development. Importantly, two autism-associated truncations, R205X and E239X, were shown to be Dyrk1a loss-of-function mutants. Studies of the truncated Dyrk1a mutants may provide new insights into the role of Dyrk1a in brain development, as well as the role of Dyrk1a loss of function in the pathophysiology of autism. Nature Publishing Group 2018 2017-02-07 /pmc/articles/PMC5822466/ /pubmed/28167836 http://dx.doi.org/10.1038/mp.2016.253 Text en Copyright © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original Article
Dang, T
Duan, W Y
Yu, B
Tong, D L
Cheng, C
Zhang, Y F
Wu, W
Ye, K
Zhang, W X
Wu, M
Wu, B B
An, Y
Qiu, Z L
Wu, B L
Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development
title Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development
title_full Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development
title_fullStr Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development
title_full_unstemmed Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development
title_short Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development
title_sort autism-associated dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822466/
https://www.ncbi.nlm.nih.gov/pubmed/28167836
http://dx.doi.org/10.1038/mp.2016.253
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