ZFIN ID: ZDB-PUB-151208-7
TAF1 Variants Are Associated with Dysmorphic Features, Intellectual Disability, and Neurological Manifestations
O'Rawe, J.A., Wu, Y., Dörfel, M.J., Rope, A.F., Au, P.Y., Parboosingh, J.S., Moon, S., Kousi, M., Kosma, K., Smith, C.S., Tzetis, M., Schuette, J.L., Hufnagel, R.B., Prada, C.E., Martinez, F., Orellana, C., Crain, J., Caro-Llopis, A., Oltra, S., Monfort, S., Jiménez-Barrón, L.T., Swensen, J., Ellingwood, S., Smith, R., Fang, H., Ospina, S., Stegmann, S., Den Hollander, N., Mittelman, D., Highnam, G., Robison, R., Yang, E., Faivre, L., Roubertie, A., Rivière, J.B., Monaghan, K.G., Wang, K., Davis, E.E., Katsanis, N., Kalscheuer, V.M., Wang, E.H., Metcalfe, K., Kleefstra, T., Innes, A.M., Kitsiou-Tzeli, S., Rosello, M., Keegan, C.E., Lyon, G.J.
Date: 2015
Source: American journal of human genetics   97: 922-32 (Journal)
Registered Authors: Davis, Erica, Katsanis, Nicholas
Keywords: TAF1, abnormal gait, developmental delay, dystonia, facial dysmorphology, intellectual disability, intergluteal crease, neurologic features, transcription
MeSH Terms:
  • Adolescent
  • Animals
  • Child
  • Child, Preschool
  • Developmental Disabilities/genetics*
  • Developmental Disabilities/metabolism
  • Developmental Disabilities/pathology
  • Disease Models, Animal
  • E-Box Elements
  • Facies
  • Family
  • Gene Expression Regulation
  • Histone Acetyltransferases/genetics*
  • Histone Acetyltransferases/metabolism
  • Humans
  • Infant
  • Inheritance Patterns
  • Intellectual Disability/genetics*
  • Intellectual Disability/metabolism
  • Intellectual Disability/pathology
  • Male
  • Mutation
  • Neurodegenerative Diseases/genetics*
  • Neurodegenerative Diseases/metabolism
  • Neurodegenerative Diseases/pathology
  • Pedigree
  • Phenotype
  • Signal Transduction
  • TATA-Binding Protein Associated Factors/genetics*
  • TATA-Binding Protein Associated Factors/metabolism
  • Transcription Factor TFIID/genetics*
  • Transcription Factor TFIID/metabolism
  • Young Adult
  • Zebrafish
PubMed: 26637982 Full text @ Am. J. Hum. Genet.
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.