English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Functional characterization of TBR1 variants in neurodevelopmental disorder

Den Hoed, J., Sollis, E., Venselaar, H., Estruch, S. B., Derizioti, P., & Fisher, S. E. (2018). Functional characterization of TBR1 variants in neurodevelopmental disorder. Scientific Reports, 8: 14279. doi:10.1038/s41598-018-32053-6.

Item is

Files

show Files
hide Files
:
Den Hoed-2018-Functional-characterization-of-tbr-.pdf (Publisher version), 2MB
Name:
Den Hoed-2018-Functional-characterization-of-tbr-.pdf
Description:
-
OA-Status:
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
2018
Copyright Info:
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.
:
41598_2018_32053_MOESM1_ESM.pdf (Supplementary material), 3MB
Name:
Electronic supplementary material
Description:
-
OA-Status:
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Den Hoed, Joery1, 2, Author           
Sollis, Elliot1, 2, Author           
Venselaar, Hanka3, Author
Estruch, Sara Busquets1, Author           
Derizioti, Pelagia1, Author           
Fisher, Simon E.1, 4, Author           
Affiliations:
1Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society, ou_792549              
2International Max Planck Research School for Language Sciences, MPI for Psycholinguistics, Max Planck Society, Nijmegen, NL, ou_1119545              
3Centre for Molecular and Biomolecular Informatics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, ou_persistent22              
4Donders Institute for Brain, Cognition and Behaviour, External Organizations, ou_55236              

Content

show
hide
Free keywords: -
 Abstract: Recurrent de novo variants in the TBR1 transcription factor are implicated in the etiology of sporadic autism spectrum disorders (ASD). Disruptions include missense variants located in the T-box DNA-binding domain and previous work has demonstrated that they disrupt TBR1 protein function. Recent screens of thousands of simplex families with sporadic ASD cases uncovered additional T-box variants in TBR1 but their etiological relevance is unclear. We performed detailed functional analyses of de novo missense TBR1 variants found in the T-box of ASD cases, assessing many aspects of protein function, including subcellular localization, transcriptional activity and protein-interactions. Only two of the three tested variants severely disrupted TBR1 protein function, despite in silico predictions that all would be deleterious. Furthermore, we characterized a putative interaction with BCL11A, a transcription factor that was recently implicated in a neurodevelopmental syndrome involving developmental delay and language deficits. Our findings enhance understanding of molecular functions of TBR1, as well as highlighting the importance of functional testing of variants that emerge from next-generation sequencing, to decipher their contributions to neurodevelopmental disorders like ASD.

Details

show
hide
Language(s): eng - English
 Dates: 2018-08-312018-09-24
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41598-018-32053-6
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Scientific Reports
  Abbreviation : Sci. Rep.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: London, UK : Nature Publishing Group
Pages: - Volume / Issue: 8 Sequence Number: 14279 Start / End Page: - Identifier: ISSN: 2045-2322
CoNE: https://pure.mpg.de/cone/journals/resource/2045-2322