De novo putative loss-of-function variants in TAF4 are associated with a neuro-developmental disorder
Janssen, Beau D E; van den Boogaard, Marie-Jose H; Lichtenbelt, Klaske; Seaby, Eleanor G; Stals, Karen; Ellard, Sian; Newbury-Ecob, Ruth; Dixit, Abhijit; Roht, Laura; Pajusalu, Sander; Õunap, Katrin; Firth, Helen V; Buckley, Michael; Wilson, Meredith; Roscioli, Tony; Tidwell, Timothy; Mao, Rong; Ennis, Sarah; Holwerda, Sjoerd J; van Gassen, Koen; van Jaarsveld, Richard H
(2022) Human mutation, volume 43, issue 12, pp. 1844 - 1851
(Article)
Abstract
TATA-binding protein associated factor 4 (TAF4) is a subunit of the Transcription Factor IID (TFIID) complex, a central player in transcription initiation. Other members of this multimeric complex have been implicated previously as monogenic disease genes in human developmental disorders. TAF4 has not been described to date as a monogenic
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disease gene. We here present a cohort of eight individuals, each carrying de novo putative loss-of-function (pLoF) variants in TAF4 and expressing phenotypes consistent with a neuro-developmental disorder (NDD). Common features include intellectual disability, abnormal behavior, and facial dysmorphisms. We propose TAF4 as a novel dominant disease gene for NDD, and coin this novel disorder “TAF4-related NDD” (T4NDD). We place T4NDD in the context of other disorders related to TFIID subunits, revealing shared features of T4NDD with other TAF-opathies.
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Keywords: human genetics, mendelian disorders, neurodevelopmental disorder, TAF4, TFIID, Genetics(clinical), Genetics, Journal Article
ISSN: 1059-7794
Publisher: Wiley-Liss Inc.
Note: Funding Information: We wish to thank the patients and families described in this manuscript. We thank the genetic diagnostic labs for providing technical support and data presentation. We thank the van Haaften Lab for fruitful discussions and manuscript review. This study was supported by funding from the Genetics Department at UMC Utrecht, the Netherlands; the Australian NHMRC Centre for Research Excellence in Neurocognition (Grant Number 1117394); LR, SP, and KÕ are supported by the Estonian Research Council grants PRG471 and MOBTP175. This study was furthermore made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK, and the Medical Research Council have also funded research infrastructure. The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support. Funding Information: We wish to thank the patients and families described in this manuscript. We thank the genetic diagnostic labs for providing technical support and data presentation. We thank the van Haaften Lab for fruitful discussions and manuscript review. This study was supported by funding from the Genetics Department at UMC Utrecht, the Netherlands; the Australian NHMRC Centre for Research Excellence in Neurocognition (Grant Number 1117394); LR, SP, and KÕ are supported by the Estonian Research Council grants PRG471 and MOBTP175. This study was furthermore made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK, and the Medical Research Council have also funded research infrastructure. The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support. Publisher Copyright: © 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.
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