Fig. 4

Each of the three DNMT genes is mutated in specific and diverse human syndromes. a DNMT3B bears recessive loss-of-function mutations in ICF syndrome type 1. b DNMT3A is mutated in dominant DNMT3A overgrowth syndrome and in subset of cases of acute myeloid leukemia and myelodysplastic syndrome. While most AML/MDS mutations affect codon 882, mutations at other positions also occur. c The RFTS domain of DNMT1 is subject to many different dominant mutations in a variable adult-onset cerebellar ataxia, deafness, dementia, and narcolepsy syndrome. The RFTS mediates interactions with replication foci during S phase (d) and with UHRF1. The positions of the amino acid substitutions within the structure of DNMT1 are shown in e. Only a subset of reported disease-associated mutations are shown for any of the three genes