Official websites use. Share sensitive information only on official, secure websites. 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. Keywords: intellectual disability, developmental delay, facial dysmorphology, TAF1, transcription, intergluteal crease, neurologic features, dystonia, abnormal gait. TFIID promotes transcriptional initiation by recognizing promoter DNA and facilitating the nucleation of other general transcription factors for assembly into a functional pre-initiation complex, 1 , 2 , 3 , 4 , 5 and it also functions as a co-activator by interacting with transcriptional activators.
A recent paper nominated TAF1 MIM: as a candidate gene for ID on the basis of segregation of missense variants in two different pedigrees; however, no clinical information other than ID was provided. Previous work in Drosophila cells has shown that TAF1 depletion increases the magnitude of the initial transcription burst and causes delay in the shutoff of transcription upon removal of the stimulus.
In addition, and consistent with the notion that TAF1 is important in controlling the binding patterns of TFIID to specific promoter regions, this study showed that the set of genes conferring increased expression were enriched with TATA-containing promoters, suggesting an association between the depletion of TAF1 and increased expression of genes with the TATA motif.
