De novo CSDE1 missense variant T595N regulates miRNA expression in a patient with a complex neurodevelopmental condition

Loss of function variants in CSDE1 have been identified in patients with neurodevelopmental disorders. De novo CSDE1 missense variant T595N was identified in an individual manifesting autistic behavior in addition to features typical of Cohen syndrome. Patient derived skin fibroblasts expressing T595N showed increased expression of HECW2. HECW2 is a ubiquitin ligase associated with neurodevelopment, and a synapse-related target of CSDE1. The E3 ligase activity of HECW2 is necessary for the downregulation of Dicer protein, a core component in the miRNA pathway that dictates miRNA expression.