Pathogenic variants are mostly de novo. In rare cases they can be inherited from a mildly affected parent. Although the number of characterized patients is still small, Le Duc et al. (2019) identified two missense variants located in the PH domain of the protein, which are associated with microcephaly. All other variants, whether missense or truncating, are associated with an increased head circumference. This phenotype has been recapitulated in homozygous knockout and haploinsufficient mouse models. Le Duc et al. (2019) suspect that PH domain variants may lead to gain-of-function, while the other variants lead to loss-of-function. Preliminary results in a Drosophila model suggest that glia cells are the main contributors to abnormal brain . While with respect to brain , Le Duc et al. (2019) noted different phenotypes depending on the type of the specific variant, the neurodevelopmental delay spectrum is the same in all probands.
WDFY3