Centromere alterations and breaks have also been found in human genetic diseases like the Immunodeficiency, Centromeric region instability, Facial anomalies syndrome (ICF), where mutations of DNA Methyl-Transferase 3 Beta (DNMT3B) (55% of reported cases), ZBTB24, CDCA7, or HELLS44,45 correlate with loss of DNA methylation, pericentromeric breaks, and rearrangements near the centromere with consequent whole-arm deletion (Fig. 1). Here, DNMT3B is linked to immunodeficiency disease.