The chromosomal instability hypothesis is mostly supported indirectly by cytogenetic findings in DNMT3B deficiency (ICF syndrome [46]), the increased rate of loss of heterozygosity in tumors formed in mice with Dnmt1 mutations [78] and the induction of fragile sites [79] and chromosome breakage [80] by DNMT1 inhibitors. The gene discussed is DNMT1; the disease is hyperinsulinemic hypoglycemia, familial, 4.