Our analysis showed that while AKT3 deletion is associated with more severe (≤3 SD) microcephaly in 1q43-q44 deletion patients, other genes may contribute to microcephaly in AKT3 intact patients with microcephaly and 1q43-44 deletion syndrome.
Our study demonstrates that AKT3 haploinsufficiency is the main driver for microcephaly, whereas HNRNPU alteration mostly drives epilepsy and determines the degree of intellectual disability.
Phenotype and genotype studies of patients with 1q44 deletion syndrome have suggested that deletion of the AKT3 gene is responsible for the microcephaly in these patients.
Mapping of deletion and translocation breakpoints in 1q44 implicates the serine/threonine kinase AKT3 in postnatal microcephaly and agenesis of the corpus callosum.