PSEN1 and histiocytic sarcoma: In families 3–6, reverse transcription polymerase chain reaction demonstrated a reduction in transcript expression in individuals with a frameshift or nonsense mutation in PSEN1 or NCSTN, indicating these mutations ultimately lead to a loss of function, leading to defective Notch signaling.32 Twenty-five familial HS case studies were reviewed and revealed 37 unique mutations in the GSC (Table 1).