Increased skewing of X chromosome inactivation in Rett syndrome patients and their mothers
Knudsen, Gun Peggy S., Neilson, Tracey C. S., Pedersen, June, Kerr, Alison, Schwartz, Marianne, Hultén, Maj A., Bailey, Mark E. S. and Orstavik, Karen Helene. (2006) Increased skewing of X chromosome inactivation in Rett syndrome patients and their mothers. EUROPEAN JOURNAL OF HUMAN GENETICS, 14 (11). pp. 1189-1194. ISSN 1018-4813Full text not available from this repository.
Official URL: http://dx.doi.org/10.1038/sj.ejhg.5201682
Rett syndrome is a largely sporadic, X-linked neurological disorder with a characteristic phenotype, but which exhibits substantial phenotypic variability. This variability has been partly attributed to an effect of X chromosome inactivation (XCI). There have been conflicting reports regarding incidence of skewed X inactivation in Rett syndrome. In rare familial cases of Rett syndrome, favourably skewed X inactivation has been found in phenotypically normal carrier mothers. We have investigated the X inactivation pattern in DNA from blood and buccal cells of sporadic Rett patients (n = 96) and their mothers (n = 84). The mean degree of skewing in blood was higher in patients (70.7%) than controls (64.9%). Unexpectedly, the mothers of these patients also had a higher mean degree of skewing in blood (70.8%) than controls. In accordance with these findings, the frequency of skewed (XCI >= 80%) X inactivation in blood was also higher in both patients (25%) and mothers (30%) than in controls (11%). To test whether the Rett patients with skewed X inactivation were daughters of skewed mothers, 49 mother - daughter pairs were analysed. Of 14 patients with skewed X inactivation, only three had a mother with skewed X inactivation. Among patients, mildly affected cases were shown to be more skewed than more severely affected cases, and there was a trend towards preferential inactivation of the paternally inherited X chromosome in skewed cases. These findings, particularly the greater degree of X inactivation skewing in Rett syndrome patients, are of potential significance in the analysis of genotype - phenotype correlations in Rett syndrome.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry
Q Science > QH Natural history > QH426 Genetics
|Journal or Publication Title:||EUROPEAN JOURNAL OF HUMAN GENETICS|
|Publisher:||NATURE PUBLISHING GROUP|
|Number of Pages:||6|
|Page Range:||pp. 1189-1194|
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