Rett Syndrome

Rett syndrome is a rare genetic neurological disorder caused by mutations in the MECP2 gene. Patients are almost exclusively females. Because MECP2 is carried on the X chromosome, one of two MECP2 copies in females is subject to random X chromosome inactivation (XCI).  In females carrying heterozygous MECP2 mutations, once the normal copy undergoes XCI, the cells will be affected due to the mutant copy. The endogenous MECP2 level is tightly regulated, which is a major hurdle towards successful gene replacement therapy.