Fiche publication
Date publication
décembre 2015
Journal
American journal of human genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence
Tous les auteurs :
O'Rawe JA, Wu Y, Dörfel MJ, Rope AF, Au PY, Parboosingh JS, Moon S, Kousi M, Kosma K, Smith CS, Tzetis M, Schuette JL, Hufnagel RB, Prada CE, Martinez F, Orellana C, Crain J, Caro-Llopis A, Oltra S, Monfort S, Jiménez-Barrón LT, 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 JB, Monaghan KG, Wang K, Davis EE, Katsanis N, Kalscheuer VM, Wang EH, Metcalfe K, Kleefstra T, Innes AM, Kitsiou-Tzeli S, Rosello M, Keegan CE, Lyon GJ
Lien Pubmed
Résumé
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.
Mots clés
Adolescent, Animals, Child, Child, Preschool, Developmental Disabilities, genetics, Disease Models, Animal, E-Box Elements, Facies, Family, Gene Expression Regulation, Histone Acetyltransferases, genetics, Humans, Infant, Inheritance Patterns, Intellectual Disability, genetics, Male, Mutation, Neurodegenerative Diseases, genetics, Pedigree, Phenotype, Signal Transduction, TATA-Binding Protein Associated Factors, genetics, Transcription Factor TFIID, genetics, Young Adult, Zebrafish
Référence
Am. J. Hum. Genet.. 2015 Dec 3;97(6):922-32
