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Original article| Volume 27, ISSUE 4, P266-270, June 2005

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X chromosome inactivation patterns in brain in Rett syndrome: implications for the disease phenotype

  • Joanne H. Gibson
    Affiliations
    Metabolic Diseases Research Unit, Western Sydney Genetics Program, Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia

    School of Paediatrics and Child Health, University of Sydney, Sydney, NSW, Australia
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  • Sarah L. Williamson
    Affiliations
    Metabolic Diseases Research Unit, Western Sydney Genetics Program, Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia

    School of Paediatrics and Child Health, University of Sydney, Sydney, NSW, Australia
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  • Susan Arbuckle
    Affiliations
    Department of Histopathology, Children's Hospital at Westmead, Sydney, NSW, Australia
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  • John Christodoulou
    Correspondence
    Corresponding author. Tel.: +61 2 9845 3452; fax: +61 2 9845 1864.
    Affiliations
    Metabolic Diseases Research Unit, Western Sydney Genetics Program, Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia

    School of Paediatrics and Child Health, University of Sydney, Sydney, NSW, Australia
    Search for articles by this author

      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)
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