HELLS and ICF syndrome: Although mutations of DNMT3B (ICF1), ZBTB24 (ICF2), CDCA7 (ICF3), and HELLS (ICF4) cause ICF syndrome, the genomic DNA methylation pattern in the de novo DNA methyltransferase–defective ICF1 patient cell lines is distinct from ICF2-4 cell lines, in which CpG-poor regions with heterochromatin features are particularly hypomethylated (46).