DCHS1 and van Maldergem syndrome: Third, in addition to providing an improved method for dCas9-mediated manipulation of (hydroxy-)methylation, we assessed the significance of our observations by validating the causal link between demethylation, up-regulation of gene expression, and regulation of corticogenesis for one paradigmatic gene containing a 5mC-loss/5hmC-gain locus: Dchs1. This gene has recently emerged as a novel regulator of brain development whose mutations cause Van Maldergem syndrome, an autosomal-recessive disorder characterized by intellectual disability and skeletal malformations (Cappello et al, 2013).