O’Rawe, Jason A, Wu, Yiyang, Dörfel, Max J, Rope, Alan F, Au, P. Y. Billie, Parboosingh, Jillian S, Moon, Sungjin, Kousi, Maria, Kosma, Konstantina, Smith, Christopher S, Tzetis, Maria, Schuette, Jane L, Hufnagel, Robert B, Prada, Carlos E, Martinez, Francisco, Orellana, Carmen, Crain, Jonathan, Caro-Llopis, Alfonso, Oltra, Silvestre, Monfort, Sandra, Jiménez-Barrón, Laura T, Swensen, Jeffrey, Ellingwood, Sara, Smith, Rosemarie, Fang, Han, Ospina, Sandra, Stegmann, Sander, Den Hollander, Nicolette, Mittelman, David, Highnam, Gareth, Robison, Reid, Yang, Edward, Faivre, Laurence, Roubertie, Agathe, Rivière, Jean-Baptiste, Monaghan, Kristin G, Wang, Kai, Davis, Erica E, Katsanis, Nicholas, Kalscheuer, Vera M, Wang, Edith H, Metcalfe, Kay, Kleefstra, Tjitske, Innes, A. Micheil, Kitsiou-Tzeli, Sophia, Rosello, Monica, Keegan, Catherine E, Lyon, Gholson J (December 2015) TAF1 Variants Are Associated with Dysmorphic Features, Intellectual Disability, and Neurological Manifestations. The American Journal of Human Genetics, 97 (6). pp. 922-932. ISSN 0002-9297
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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | intellectual disability developmental delay facial dysmorphology TAF1 transcription intergluteal crease neurologic features dystonia abnormal gait |
| Subjects: | diseases & disorders > congenital hereditary genetic diseases diseases & disorders > mental disorders diseases & disorders > mental disorders > genetic disorders |
| CSHL Authors: | |
| Communities: | CSHL labs > Lyon lab |
| Depositing User: | Matt Covey |
| Date: | 3 December 2015 |
| Date Deposited: | 08 Dec 2015 17:40 |
| Last Modified: | 17 Feb 2016 22:03 |
| PMCID: | PMC4678794 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/32023 |
Actions (login required)
 |
Administrator's edit/view item |