Homo sapiens Raw sequence reads

We describe an X-linked genetic syndrome associated with mutations in TAF1 presenting with global developmental delay, intellectual disability, characteristic facial dysmorphology, generalized hypotonia, and variable neurologic features, all in male cases. Simultaneous studies using diverse strategies led to nine families with overlapping clinical presentations and with de novo or maternally inherited missense mutations. Two additional families harboring large duplications involving TAF1 were also found to share phenotypic overlap with the probands harboring missense mutations, but they also demonstrated a severe neurodegeneration phenotype. Functional analysis with RNA-seq for one of the families suggest that the phenotype is associated with down regulation of a set of genes notably enriched for genes regulated by E-box proteins, and knockdown and mutant studies for this gene in zebrafish have a quantifiable, albeit small, effect on a neuronal phenotype. Our results implicate mutations in TAF1 as playing a critical role in the development of this X-linked intellectual disability syndrome.