@article{3087768,
    title = "TAF1 Variants Are Associated with Dysmorphic Features, Intellectual Disability, and Neurological Manifestations",
    author = "O'Rawe, J.A. and Wu, Y. and Dörfel, M.J. and Rope, A.F. and Au, P.Y.B. and Parboosingh, J.S. and Moon, S. and Kousi, M. and Kosma, K. and Smith, C.S. and Tzetis, M. and Schuette, J.L. and Hufnagel, R.B. and Prada, C.E. and Martinez, F. and Orellana, C. and Crain, J. and Caro-Llopis, A. and Oltra, S. and Monfort, S. and Jiménez-Barrón, L.T. and Swensen, J. and Ellingwood, S. and Smith, R. and Fang, H. and Ospina, S. and Stegmann, S. and Den Hollander, N. and Mittelman, D. and Highnam, G. and Robison, R. and Yang, E. and Faivre, L. and Roubertie, A. and Rivière, J.-B. and Monaghan, K.G. and Wang, K. and Davis, E.E. and Katsanis, N. and Kalscheuer, V.M. and Wang, E.H. and Metcalfe, K. and Kleefstra, T. and Innes, A.M. and Kitsiou-Tzeli, S. and Rosello, M. and Keegan, C.E. and Lyon, G.J.",
    journal = "American Journal of Human Genetics",
    year = "2015",
    volume = "97",
    number = "6",
    pages = "922-932",
    publisher = "Cell Press",
    issn = "0002-9297, 1537-6605",
    doi = "10.1016/j.ajhg.2015.11.005",
    keywords = "e box protein;  protein;  TATA binding protein associated factor;  transcription factor;  unclassified drug;  histone acetyltransferase;  TATA binding protein associated factor;  TATA-binding protein associated factor 250 kDa;  transcription factor IID, adolescent;  Article;  child;  clinical article;  clinical assessment;  clinical evaluation;  clinical feature;  developmental disorder;  down regulation;  face dysmorphia;  family assessment;  gene duplication;  gene mutation;  genetic association;  genetic disorder;  genetic screening;  human;  intellectual impairment;  male;  muscle hypotonia;  nerve degeneration;  neurologic disease;  phenotypic variation;  preschool child;  priority journal;  recessive inheritance;  RNA sequence;  school child;  single nucleotide polymorphism;  zebra fish;  animal;  degenerative disease;  disease model;  E box element;  facies;  family;  gene expression regulation;  genetics;  infant;  inheritance;  intellectual impairment;  metabolism;  mutation;  pathology;  pedigree;  phenotype;  signal transduction;  young adult, Adolescent;  Animals;  Child;  Child, Preschool;  Developmental Disabilities;  Disease Models, Animal;  E-Box Elements;  Facies;  Family;  Gene Expression Regulation;  Histone Acetyltransferases;  Humans;  Infant;  Inheritance Patterns;  Intellectual Disability;  Male;  Mutation;  Neurodegenerative Diseases;  Pedigree;  Phenotype;  Signal Transduction;  TATA-Binding Protein Associated Factors;  Transcription Factor TFIID;  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. © 2015 The Authors."
}