A large proportion of the whole exome-sequenced cases (15/46) harbor a single rare or novel deleterious germline variant in a gene from the PI3K/Akt signaling cascade: newly identified candidate susceptibility genes included PIK3CD, MTOR, EP300, and NFRKB. The PI3K/Akt pathway is among the most frequently somatically mutated in cancer [86]. The gene discussed is EP300; the disease is cancer.