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De novo variants in GATAD2A in individuals with a neurodevelopmental disorder: GATAD2A-related neurodevelopmental disorder

GATA zinc finger domain containing 2A (GATAD2A) is a subunit of the nucleosome remodeling and deacetylase (NuRD) complex. NuRD is known to regulate gene expression during neural development and other processes. The NuRD complex modulates chromatin status through histone deacetylation and ATP-depende...

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Autores principales: Werren, Elizabeth A., Guxholli, Alba, Jones, Natasha, Wagner, Matias, Hannibal, Iris, Granadillo, Jorge L., Tyndall, Amanda V., Moccia, Amanda, Kuehl, Ryan, Levandoski, Kristin M., Day-Salvatore, Debra L., Wheeler, Marsha, Chong, Jessica X., Bamshad, Michael J., Innes, A. Micheil, Pierson, Tyler Mark, Mackay, Joel P., Bielas, Stephanie L., Martin, Donna M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10172836/
https://www.ncbi.nlm.nih.gov/pubmed/37181331
http://dx.doi.org/10.1016/j.xhgg.2023.100198
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author Werren, Elizabeth A.
Guxholli, Alba
Jones, Natasha
Wagner, Matias
Hannibal, Iris
Granadillo, Jorge L.
Tyndall, Amanda V.
Moccia, Amanda
Kuehl, Ryan
Levandoski, Kristin M.
Day-Salvatore, Debra L.
Wheeler, Marsha
Chong, Jessica X.
Bamshad, Michael J.
Innes, A. Micheil
Pierson, Tyler Mark
Mackay, Joel P.
Bielas, Stephanie L.
Martin, Donna M.
author_facet Werren, Elizabeth A.
Guxholli, Alba
Jones, Natasha
Wagner, Matias
Hannibal, Iris
Granadillo, Jorge L.
Tyndall, Amanda V.
Moccia, Amanda
Kuehl, Ryan
Levandoski, Kristin M.
Day-Salvatore, Debra L.
Wheeler, Marsha
Chong, Jessica X.
Bamshad, Michael J.
Innes, A. Micheil
Pierson, Tyler Mark
Mackay, Joel P.
Bielas, Stephanie L.
Martin, Donna M.
author_sort Werren, Elizabeth A.
collection PubMed
description GATA zinc finger domain containing 2A (GATAD2A) is a subunit of the nucleosome remodeling and deacetylase (NuRD) complex. NuRD is known to regulate gene expression during neural development and other processes. The NuRD complex modulates chromatin status through histone deacetylation and ATP-dependent chromatin remodeling activities. Several neurodevelopmental disorders (NDDs) have been previously linked to variants in other components of NuRD’s chromatin remodeling subcomplex (NuRDopathies). We identified five individuals with features of an NDD that possessed de novo autosomal dominant variants in GATAD2A. Core features in affected individuals include global developmental delay, structural brain defects, and craniofacial dysmorphology. These GATAD2A variants are predicted to affect protein dosage and/or interactions with other NuRD chromatin remodeling subunits. We provide evidence that a GATAD2A missense variant disrupts interactions of GATAD2A with CHD3, CHD4, and CHD5. Our findings expand the list of NuRDopathies and provide evidence that GATAD2A variants are the genetic basis of a previously uncharacterized developmental disorder.
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spelling pubmed-101728362023-05-12 De novo variants in GATAD2A in individuals with a neurodevelopmental disorder: GATAD2A-related neurodevelopmental disorder Werren, Elizabeth A. Guxholli, Alba Jones, Natasha Wagner, Matias Hannibal, Iris Granadillo, Jorge L. Tyndall, Amanda V. Moccia, Amanda Kuehl, Ryan Levandoski, Kristin M. Day-Salvatore, Debra L. Wheeler, Marsha Chong, Jessica X. Bamshad, Michael J. Innes, A. Micheil Pierson, Tyler Mark Mackay, Joel P. Bielas, Stephanie L. Martin, Donna M. HGG Adv Article GATA zinc finger domain containing 2A (GATAD2A) is a subunit of the nucleosome remodeling and deacetylase (NuRD) complex. NuRD is known to regulate gene expression during neural development and other processes. The NuRD complex modulates chromatin status through histone deacetylation and ATP-dependent chromatin remodeling activities. Several neurodevelopmental disorders (NDDs) have been previously linked to variants in other components of NuRD’s chromatin remodeling subcomplex (NuRDopathies). We identified five individuals with features of an NDD that possessed de novo autosomal dominant variants in GATAD2A. Core features in affected individuals include global developmental delay, structural brain defects, and craniofacial dysmorphology. These GATAD2A variants are predicted to affect protein dosage and/or interactions with other NuRD chromatin remodeling subunits. We provide evidence that a GATAD2A missense variant disrupts interactions of GATAD2A with CHD3, CHD4, and CHD5. Our findings expand the list of NuRDopathies and provide evidence that GATAD2A variants are the genetic basis of a previously uncharacterized developmental disorder. Elsevier 2023-04-20 /pmc/articles/PMC10172836/ /pubmed/37181331 http://dx.doi.org/10.1016/j.xhgg.2023.100198 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Werren, Elizabeth A.
Guxholli, Alba
Jones, Natasha
Wagner, Matias
Hannibal, Iris
Granadillo, Jorge L.
Tyndall, Amanda V.
Moccia, Amanda
Kuehl, Ryan
Levandoski, Kristin M.
Day-Salvatore, Debra L.
Wheeler, Marsha
Chong, Jessica X.
Bamshad, Michael J.
Innes, A. Micheil
Pierson, Tyler Mark
Mackay, Joel P.
Bielas, Stephanie L.
Martin, Donna M.
De novo variants in GATAD2A in individuals with a neurodevelopmental disorder: GATAD2A-related neurodevelopmental disorder
title De novo variants in GATAD2A in individuals with a neurodevelopmental disorder: GATAD2A-related neurodevelopmental disorder
title_full De novo variants in GATAD2A in individuals with a neurodevelopmental disorder: GATAD2A-related neurodevelopmental disorder
title_fullStr De novo variants in GATAD2A in individuals with a neurodevelopmental disorder: GATAD2A-related neurodevelopmental disorder
title_full_unstemmed De novo variants in GATAD2A in individuals with a neurodevelopmental disorder: GATAD2A-related neurodevelopmental disorder
title_short De novo variants in GATAD2A in individuals with a neurodevelopmental disorder: GATAD2A-related neurodevelopmental disorder
title_sort de novo variants in gatad2a in individuals with a neurodevelopmental disorder: gatad2a-related neurodevelopmental disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10172836/
https://www.ncbi.nlm.nih.gov/pubmed/37181331
http://dx.doi.org/10.1016/j.xhgg.2023.100198
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