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

Jason A. O'Rawe, Yiyang Wu, Max J. Dörfel, Alan F. Rope, P. Y.Billie Au, Jillian S. Parboosingh, Sungjin Moon, Maria Kousi, Konstantina Kosma, Christopher S. Smith, Maria Tzetis, Jane L. Schuette, Robert B. Hufnagel, Carlos E. Prada, Francisco Martinez, Carmen Orellana, Jonathan Crain, Alfonso Caro-Llopis, Silvestre Oltra, Sandra MonfortLaura T. Jiménez-Barrón, Jeffrey Swensen, Sara Ellingwood, Rosemarie Smith, Han Fang, Sandra Ospina, Sander Stegmann, Nicolette Den Hollander, David Mittelman, Gareth Highnam, Reid Robison, Edward Yang, Laurence Faivre, Agathe Roubertie, Jean Baptiste Rivière, Kristin G. Monaghan, Kai Wang, Erica E. Davis, Nicholas Katsanis, Vera M. Kalscheuer, Edith H. Wang, Kay Metcalfe, Tjitske Kleefstra, A. Micheil Innes, Sophia Kitsiou-Tzeli, Monica Rosello, Catherine E. Keegan, Gholson J. Lyon

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)922-932
Number of pages11
JournalAmerican Journal of Human Genetics
Issue number6
StatePublished - Dec 3 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'TAF1 Variants Are Associated with Dysmorphic Features, Intellectual Disability, and Neurological Manifestations'. Together they form a unique fingerprint.

Cite this