EBP and X-linked disease: If the wild-type X chromosome is inactivated in a high percentage of cells, skewed X inactivation may have a significant effect on the severity of X-linked disease in heterozygous females.[9,10,13] Shirahama et al evaluated the potential effects of methylation and skewed X inactivation in CDPX2.[10] Two patients with X-chromosome inactivation presented severe phenotypes, whereas their mothers presented mild phenotypes.