Mild to moderate neurodevelopmental disorders (NDD) are poorly understood and late diagnosis and interventions result in a high burden for the society and health system.
Our project investigates the gene WDFY3, a monogenic cause for moderate NDD. In human probands and in a mouse model we have shown that variants affecting WDFY3 may result in either increased, or decreased brain size. We hypothesize that the different outcomes depend on gain- or loss-of-function of the encoded protein. We will test this by introducing the variants in Drosophila followed by molecular and morphologic characterization of brains and neurons from multiple mutants. This will aid the understanding of the underlying mechanism. The approach could be applied for additional genes, and hence uncover further NDD pathomechanisms.