DNA undermethylation is a characteristic feature of ICF syndrome and has been 
implicated in the formation of the juxtacentromeric chromosomal abnormalities of 
this rare syndrome. We have previously shown that in female ICF patients the 
inactive X chromosome (Xi) is also undermethylated. This result was unexpected 
since female ICF patients are not more severely affected than male patients. 
Here we show that CpG island methylation is abnormal in some ICF patients but in 
other ICF patients, the difference in methylation pattern between Xi and Xa 
(active X) is maintained. The consequences of Xi undermethylation on gene 
expression were investigated by enzyme assays. They showed that significant gene 
expression did not correlate with CpG island methylation status. The widespread 
Xi undermethylation does not affect overall Xi replication timing and does not 
prevent Barr body formation suggesting that a normal methylation pattern is not 
required for normal chromatin organization of Xi. Molecular investigation of 
some X-chromosome intron regions showed that the methylation changes in ICF 
female patients extend to non CpG islands sequences. Our results suggest that 
the genetic alteration of DNA methylation in ICF syndrome has little consequence 
on X chromosome gene expression and chromatin organization.