Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability
- Author
- Maria del Rocio Pérez Baca (UGent) , Eva Jacobs, Lies Vantomme (UGent) , Pontus LeBlanc (UGent) , Elke Bogaert (UGent) , Annelies Dheedene (UGent) , Laurenz De Cock (UGent) , Sadegheh Haghshenas, Aidin Foroutan, Michael A Levy, Jennifer Kerkhof, Haley McConkey, Chun-An Chen, Nurit Assia Batzir, Xia Wang, María Palomares, Marieke Carels (UGent) , Bart Dermaut (UGent) , Bekim Sadikovic, Björn Menten (UGent) , Bo Yuan, Sarah Vergult (UGent) , Bert Callewaert (UGent) , ZFHX3 consortium and Olivier Vanakker (UGent)
- Organization
- Project
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- Functional validation of cis-regulatory elements of respectively MEF2C and FOXG1
- Unraveling the role of MYT1L in intellectual disability: an integrated functional genetic approach
- A multi-omics approach to address the role of ZFHX3 in neuronal development
- Addressing the missing heritability in rare disorders
- Unraveling the role of the KEOPS complex in Galloway-Mowat syndrome
- Study of the molecular background and pathophysiology of monogenic disorders with structural cardiovasuclar anomalies
- Abstract
- Neurodevelopmental disorders (NDDs) result from impaired development and functioning of the brain. Here, we identify loss-of-function (LoF) variation in ZFHX3 as a cause for syndromic intellectual disability (ID). ZFHX3 is a zinc-finger homeodomain transcription factor involved in various biological processes, including cell differentiation and tumorigenesis. We describe 42 individuals with protein-truncating variants (PTVs) or (partial) deletions of ZFHX3, exhibiting variable intellectual disability and autism spectrum disorder, recurrent facial features, relative short stature, brachydactyly, and, rarely, cleft palate. ZFHX3 LoF associates with a specific methylation profile in whole blood extracted DNA. Nuclear abundance of ZFHX3 increases during human brain development and neuronal differentiation. ZFHX3 was found to interact with the chromatin remodeling BRG1/Brm-associated factor complex and the cleavage and polyadenylation complex, suggesting a function in chromatin remodeling and mRNA processing. Furthermore, ChIP-seq for ZFHX3 revealed that it predominantly binds promoters of genes involved in nervous system development. We conclude that loss-of-function variants in ZFHX3 are a cause of syndromic ID associating with a specific DNA methylation profile.
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HRPYJ39WMPEEMCP3F5T02R52
- MLA
- Pérez Baca, Maria del Rocio, et al. “Haploinsufficiency of ZFHX3, Encoding a Key Player in Neuronal Development, Causes Syndromic Intellectual Disability.” AMERICAN JOURNAL OF HUMAN GENETICS, vol. 111, no. 3, 2024, pp. 509–28, doi:10.1016/j.ajhg.2024.01.013.
- APA
- Pérez Baca, M. del R., Jacobs, E., Vantomme, L., LeBlanc, P., Bogaert, E., Dheedene, A., … Vanakker, O. (2024). Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability. AMERICAN JOURNAL OF HUMAN GENETICS, 111(3), 509–528. https://doi.org/10.1016/j.ajhg.2024.01.013
- Chicago author-date
- Pérez Baca, Maria del Rocio, Eva Jacobs, Lies Vantomme, Pontus LeBlanc, Elke Bogaert, Annelies Dheedene, Laurenz De Cock, et al. 2024. “Haploinsufficiency of ZFHX3, Encoding a Key Player in Neuronal Development, Causes Syndromic Intellectual Disability.” AMERICAN JOURNAL OF HUMAN GENETICS 111 (3): 509–28. https://doi.org/10.1016/j.ajhg.2024.01.013.
- Chicago author-date (all authors)
- Pérez Baca, Maria del Rocio, Eva Jacobs, Lies Vantomme, Pontus LeBlanc, Elke Bogaert, Annelies Dheedene, Laurenz De Cock, Sadegheh Haghshenas, Aidin Foroutan, Michael A Levy, Jennifer Kerkhof, Haley McConkey, Chun-An Chen, Nurit Assia Batzir, Xia Wang, María Palomares, Marieke Carels, Bart Dermaut, Bekim Sadikovic, Björn Menten, Bo Yuan, Sarah Vergult, Bert Callewaert, ZFHX3 consortium, and Olivier Vanakker. 2024. “Haploinsufficiency of ZFHX3, Encoding a Key Player in Neuronal Development, Causes Syndromic Intellectual Disability.” AMERICAN JOURNAL OF HUMAN GENETICS 111 (3): 509–528. doi:10.1016/j.ajhg.2024.01.013.
- Vancouver
- 1.Pérez Baca M del R, Jacobs E, Vantomme L, LeBlanc P, Bogaert E, Dheedene A, et al. Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability. AMERICAN JOURNAL OF HUMAN GENETICS. 2024;111(3):509–28.
- IEEE
- [1]M. del R. Pérez Baca et al., “Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability,” AMERICAN JOURNAL OF HUMAN GENETICS, vol. 111, no. 3, pp. 509–528, 2024.
@article{01HRPYJ39WMPEEMCP3F5T02R52,
abstract = {{Neurodevelopmental disorders (NDDs) result from impaired development and functioning of the brain. Here, we identify loss-of-function (LoF) variation in ZFHX3 as a cause for syndromic intellectual disability (ID). ZFHX3 is a zinc-finger homeodomain transcription factor involved in various biological processes, including cell differentiation and tumorigenesis. We describe 42 individuals with protein-truncating variants (PTVs) or (partial) deletions of ZFHX3, exhibiting variable intellectual disability and autism spectrum disorder, recurrent facial features, relative short stature, brachydactyly, and, rarely, cleft palate. ZFHX3 LoF associates with a specific methylation profile in whole blood extracted DNA. Nuclear abundance of ZFHX3 increases during human brain development and neuronal differentiation. ZFHX3 was found to interact with the chromatin remodeling BRG1/Brm-associated factor complex and the cleavage and polyadenylation complex, suggesting a function in chromatin remodeling and mRNA processing. Furthermore, ChIP-seq for ZFHX3 revealed that it predominantly binds promoters of genes involved in nervous system development. We conclude that loss-of-function variants in ZFHX3 are a cause of syndromic ID associating with a specific DNA methylation profile.}},
author = {{Pérez Baca, Maria del Rocio and Jacobs, Eva and Vantomme, Lies and LeBlanc, Pontus and Bogaert, Elke and Dheedene, Annelies and De Cock, Laurenz and Haghshenas, Sadegheh and Foroutan, Aidin and Levy, Michael A and Kerkhof, Jennifer and McConkey, Haley and Chen, Chun-An and Batzir, Nurit Assia and Wang, Xia and Palomares, María and Carels, Marieke and Dermaut, Bart and Sadikovic, Bekim and Menten, Björn and Yuan, Bo and Vergult, Sarah and Callewaert, Bert and consortium, ZFHX3 and Vanakker, Olivier}},
issn = {{0002-9297}},
journal = {{AMERICAN JOURNAL OF HUMAN GENETICS}},
language = {{eng}},
number = {{3}},
pages = {{509--528}},
title = {{Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability}},
url = {{http://doi.org/10.1016/j.ajhg.2024.01.013}},
volume = {{111}},
year = {{2024}},
}
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