Recent work by Bicknell et al. [88,89] has shown that point mutations in the human ORC1, ORC4, ORC6, CDT1 and CDC6 genes are associated with Meier-Gorlin syndrome, a form of primordial dwarfism, and several of these mutations were determined to interfere with proper pre-RC formation. This evidence concerns the gene ORC4 and Meier-Gorlin syndrome.