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  TAF1 Variants Are Associated with Dysmorphic Features, Intellectual Disability, and Neurological Manifestations

O'Rawe, J. A., Wu, Y., Dorfel, M. J., Rope, A. F., Au, P. Y., Parboosingh, J. S., et al. (2015). TAF1 Variants Are Associated with Dysmorphic Features, Intellectual Disability, and Neurological Manifestations. The American Journal of Human Genetics, 97(6), 922-932. doi:10.1016/j.ajhg.2015.11.005.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-D03B-3 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-D03C-2
Genre: Journal Article

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© 2015 The Authors

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 Creators:
O'Rawe, J. A., Author
Wu, Y., Author
Dorfel, M. J., Author
Rope, A. F., Author
Au, P. Y., Author
Parboosingh, J. S., Author
Moon, S., Author
Kousi, M., Author
Kosma, K., Author
Smith, C. S., Author
Tzetis, M., Author
Schuette, J. L., Author
Hufnagel, R. B., Author
Prada, C. E., Author
Martinez, F., Author
Orellana, C., Author
Crain, J., Author
Caro-Llopis, A., Author
Oltra, S., Author
Monfort, S., Author
Jimenez-Barron, L. T., AuthorSwensen, J., AuthorEllingwood, S., AuthorSmith, R., AuthorFang, H., AuthorOspina, S., AuthorStegmann, S., AuthorDen Hollander, N., AuthorMittelman, D., AuthorHighnam, G., AuthorRobison, R., AuthorYang, E., AuthorFaivre, L., AuthorRoubertie, A., AuthorRiviere, J. B., AuthorMonaghan, K. G., AuthorWang, K., AuthorDavis, E. E., AuthorKatsanis, N., AuthorKalscheuer, V. M.1, Author              Wang, E. H., AuthorMetcalfe, K., AuthorKleefstra, T., AuthorInnes, A. M., AuthorKitsiou-Tzeli, S., AuthorRosello, M., AuthorKeegan, C. E., AuthorLyon, G. J., Author more..
Affiliations:
1Chromosome Rearrangements and Disease (Vera Kalscheuer), Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385702              

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Free keywords: Adolescent Animals Child Child, Preschool Developmental Disabilities/*genetics/metabolism/pathology Disease Models, Animal E-Box Elements Facies Family Gene Expression Regulation Histone Acetyltransferases/*genetics/metabolism Humans Infant Inheritance Patterns Intellectual Disability/*genetics/metabolism/pathology Male Mutation Neurodegenerative Diseases/*genetics/metabolism/pathology Pedigree Phenotype Signal Transduction TATA-Binding Protein Associated Factors/*genetics/metabolism Transcription Factor TFIID/*genetics/metabolism Young Adult Zebrafish
 Abstract: We describe an X-linked genetic syndrome associated with mutations in TAF1 and manifesting with global developmental delay, intellectual disability (ID), characteristic facial dysmorphology, generalized hypotonia, and variable neurologic features, all in male individuals. Simultaneous studies using diverse strategies led to the identification of nine families with overlapping clinical presentations and affected by de novo or maternally inherited single-nucleotide changes. Two additional families harboring large duplications involving TAF1 were also found to share phenotypic overlap with the probands harboring single-nucleotide changes, but they also demonstrated a severe neurodegeneration phenotype. Functional analysis with RNA-seq for one of the families suggested that the phenotype is associated with downregulation of a set of genes notably enriched with genes regulated by E-box proteins. In addition, knockdown and mutant studies of this gene in zebrafish have shown a quantifiable, albeit small, effect on a neuronal phenotype. Our results suggest that mutations in TAF1 play a critical role in the development of this X-linked ID syndrome.

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Language(s): eng - English
 Dates: 2015-12-03
 Publication Status: Published in print
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.ajhg.2015.11.005
ISSN: 1537-6605 (Electronic)0002-9297 (Print)
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Title: The American Journal of Human Genetics
  Other : Am. J. Hum. Genet.
Source Genre: Journal
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Publ. Info: American Society of Human Genetics
Pages: - Volume / Issue: 97 (6) Sequence Number: - Start / End Page: 922 - 932 Identifier: ISSN: 0002-9297
CoNE: https://pure.mpg.de/cone/journals/resource/954925377893_1