Although γ-secretase is composed of presenilin, presenilin enhancer-2, nicastrin, and anterior pharynx defective encoded by PSEN1/PSEN2, PSENEN, NCSTN, and APH1A/APH1B, respectively (31), no disease-causing mutations in PSEN2, APH1A, or APH1B have been identified in HS patients (16). Here, PSEN2 is linked to histiocytic sarcoma.