Three cases (T12, T18 and T28) showed a hypermutated profile compared to the rest of the cohort (mean number of somatic variants = 35.3 vs 6.4, p-value < 0.0001) (Supplementary Fig. 1); further IHC analysis of mismatch repair (MMR) proteins showed the loss of PMS2 and MLH1 expression in case T12 and T18, and loss of MSH2 and MSH6 expression in case T28, confirming the occurrence of MMR-deficiency in these hypermutated cases (Supplementary Fig. 2). This evidence concerns the gene PMS2 and hyperinsulinemic hypoglycemia, familial, 4.