NEITHER UNIPARENTAL DISOMY NOR SKEWED X-INACTIVATION EXPLAINS RETT-SYNDROME

The locus DXS255 was studied using the probe M27 beta in ten probands with Rett syndrome and in eight of their families. No evidence of unip arental disomy of the X chromosome was detected, as all informative pr obands had inherited an allele from each of their parents. Differentia l methylation of a CCGG site within the DXS255 locus as shown by diges tion with MspI/HpaII, revealed moderate skewing of X-inactivation favo uring the maternal allele in two of the probands. Random X-inactivatio n was present in all mothers tested and in two unaffected sisters. Thr ee of four unaffected siblings had inherited the same maternal allele at DXS255.