Alterations in replication timing of X-chromosome bands in Rett syndrome

A cytogenetic study has been carried out on 30 girls affected with Rett syndrome, 35 of their family members and 25 unrelated healthy control females. Karyotyping at the 850 band level revealed no detectable chromosome abnormalities in either the affected girls or their families. Observations on the sequence of the appearance of early replicating bands on both the active and the inactive X-chromosome demonstrated the same replication patterns in all of the groups investigated with the exception that band Xp21 appeared with greater frequency in the Rett syndrome cells. A degree of variation was detected both between and within the subjects when the timing of the latest bands to replicate was investigated for the active X, but the same consensus order was obtained for all groups. A comparable number of elongated X-chromosomes was found in the girls with Rett syndrome (8%) when compared to their mothers (12%) when synchronized cells were treated with a short pulse of BrdU. If a disturbance in X-inactivation does contribute to the aetiology of Rett syndrome, it is at a level which is not detected by observations on the relative timing of replication of chromosome bands.