POLE and hyperinsulinemic hypoglycemia, familial, 4: When the effect of the POLE exonuclease double mutated allele p.(Asp275Ala/Glu277Ala) in MMR-deficient HCT116 cells was looked into in another study, MMR deficiency was reported to be necessary for the ultra-mutator phenotype associated with PPAP (Hodel et al. 2018).