Similarly, a recent whole-genome sequencing study on families with two glioma cases each identified POLE/POLD1 germline nonsense variants in glioma patients from three of 189 (1.6%) families of the exploratory cohort [35], although it is controversial whether POLE/POLD1 loss-of-function variants are pathogenic for PPAP [9]. This evidence concerns the gene POLD1 and central nervous system cancer.