X chromosome-inactivation patterns in patients with Rett syndrome

Hum Genet. 1998 Mar;102(3):319-21. doi: 10.1007/s004390050698.


Rett syndrome (RS) is a complex and severely disabling neurologic disorder, restricted to females. As non-random X inactivation could indicate that the X chromosome has a role in the etiology of the syndrome, we performed molecular analysis based on the differential methylation of the active and inactive X chromosomes with probe M27beta, taking into account the parental origin of the two Xs, in 24 RS girls (including a pair of concordant monozygote twins), 22 mothers, and a control group of 30 normal women. The results showed a significantly (Fisher's exact test) increased frequency of skewed X inactivation in lymphocytes from 15/23 RS compared with 4/22 mothers (P = 0.0031) and 6/30 controls (P = 0.0021). Our results, together with those from the literature, showed that as a group, RS patients are apparently more prone to skewed X inactivation than their mothers and normal controls, and this suggests that the X chromosome is somehow involved in RS etiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Methylation
  • Diseases in Twins / genetics
  • Dosage Compensation, Genetic*
  • Female
  • Humans
  • Rett Syndrome / genetics*
  • Twins, Monozygotic