A primary role for Dnmt3b in Xi CGI methylation is consistent with a previous study that showed reduced Xi CGI methylation in lymphoblastoid cell lines from females with immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, which is caused by mutations in the human DNMT3B gene (Hansen et al., 2000; Hansen et al., 1999). Here, DNMT3B is linked to immunodeficiency disease.