CDC45 and craniosynostosis: CDC45, an essential component of the preinitiation complex (preIC), the next step in the initiation pathway, has also been associated with MGORS and/or craniosynostosis.12 CDC45 interacts with GINS1-4 and the MCM helicase to form the CMG helicase, which once activated by these interactions, unwinds DNA to allow polymerase access and commencement of DNA replication.13 Together, these genetic findings strongly support the notion that MGORS is due to disruption of origin licencing and firing in the earliest steps of DNA replication.