Abstract
X-chromosome inactivation (XCI) is random in the majority of patients with classical
Rett syndrome (RTT). Preferential inactivation of the X chromosome with the mutated
MECP2 gene is found in mildly symptomatic or asymptomatic carrier females. These findings
lead to a hypothesis that random XCI is causally involved in the pathogenesis of RTT
in heterozygous females. It is the cluster of functionally defective nerve cells lacking
fully functional MeCP2 generated by inactivation of normal MECP2 allele that causes the wide spectrum of RTT symptoms. Thus, RTT is a rare human disease
manifestation which is triggered most probably by random XCI.
Keywords
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© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
