Therefore, within the PHS hypothesis, mast cells have affinitive receptors for external pathogenic proteins, and specific or cross-reactive IgEs target the antigens bound to receptors expressed on the mast cells/basophils and trigger immune responses, rather than known action of the antigens which induce crosslinking of antigen-specific IgE bound to high affinity receptors for IgE on the mast cells’ surface. The gene discussed is IGHE; the disease is Pallister-Hall syndrome.