Increased skewing of X chromosome inactivation in Rett syndrome patients and their mothers

摘要: Rett syndrome is a largely sporadic, X-linked neurological disorder with characteristic phenotype, but which exhibits substantial phenotypic variability. This variability has been partly attributed to an effect of X chromosome inactivation (XCI). There have conflicting reports regarding incidence skewed in syndrome. In rare familial cases syndrome, favourably found phenotypically normal carrier mothers. We investigated the pattern DNA from blood and buccal cells sporadic patients (n=96) their mothers (n=84). The mean degree skewing was higher (70.7%) than controls (64.9%). Unexpectedly, these also had (70.8%) controls. accordance findings, frequency (XCI ≥80%) both (25%) (30%) (11%). To test whether were daughters mothers, 49 mother–daughter pairs analysed. Of 14 inactivation, only three mother inactivation. Among patients, mildly affected shown be more severely cases, there trend towards preferential paternally inherited cases. These particularly greater are potential significance analysis genotype–phenotype correlations