DNA Methylation and Replication: Implications for the “Deletion Hotspot” Region of FMR1

Abstract
Expansion and hyper-methylation of a CGG repeat tract are the main causes of fragile X syndrome (FRAXA). In some rare instances, FRAXA patients harbor not only an expanded CGG tract, but a deletion encompassing the CGG repeat and flanking sequences as well. Through the use of an SV40 primate replication system, it was possible to determine that CpG methylation and DNA replication may actually mediate the formation of these rare events. Also, the genetically stabilizing AGG interruptions can be lost by replication-mediated CGG deletions.