Abstract
Rett syndrome is an X-linked dominant neurodevelopmental disorder primarily affecting
girls. About 80% of classic Rett syndrome is caused by mutations in the gene for methyl-CpG-binding
protein (MeCP2) in Xq28. MeCP2 links DNA methylation to transcriptional repression,
and MECP2 mutations likely cause partial or complete loss of function of the protein, leading
to inappropriate transcription of downstream genes at critical times in brain development.
More severe and milder variant forms can all be caused by similar mutations. Most
classic Rett syndrome patients have random X-chromosome inactivation (XCI), but skewed
patterns are present in a few. All asymptomatic or mildly mentally delayed female
carriers studied to date have non-random XCI patterns, suggesting that this attenuates
the deleterious effects of the MECP2 mutations in these women. The finding of non-random XCI patterns in some patients
with very early truncations is consistent with this observation and supports that
many mutations could cause partial and not complete loss of function. Our observation
that the mutant mRNA is stable in three patients with truncating mutations supports
this possibility. Further studies will have to be performed to better understand the
functional consequences of MECP2 mutations in RTT.
Keywords
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© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
