Abstract
Skewed X chromosome inactivation (XCI) has been implicated in modulating the severity
of Rett syndrome (RTT), although studies by different groups have yielded conflicting
results. In this study we have characterised the XCI pattern in various neuroanatomical
regions of nine RTT brains and non-neural tissue in two of these patients to determine
whether or not variable XCI patterns occur in different brain regions or somatic tissues
of the same patient. The mean XCI patterns for frontal and occipital cortex were compared
between RTT and control subjects, and showed no significant differences when comparing
RTT frontal to control frontal cortex or RTT occipital to control occipital cortex.
However, one RTT subject displayed variability across the different neuroanatomical
regions of the brain and skewing in some non-neural tissues. This observation adds
another dimension to the epigenetic factors that may contribute to the phenotype in
RTT. It also mandates that caution should be exercised in factoring XCI, including
assumptions based on the blood XCI pattern, into the development of phenotype–genotype
correlations.
Keywords
Abbreviations:
XCI (X chromosome inactivation), RTT (Rett syndrome), AR (androgen receptor), BSA (bovine serum albumin), GTP (guanine triphosphate), MBD (methyl-binding domain), TRD-NLS (transcription repressor domain - nuclear localisation signal)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
July 11,
2004
Received in revised form:
June 23,
2004
Received:
March 22,
2004
Identification
Copyright
© 2004 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
