The mutations that cause the ATRX syndrome are often located within the putative ATPase/helicase domain and the PHD motif of ADD domain [2,5,34], whereas tumorigenic mutations of ATRX are randomly localized point mutations, determining protein loss of function (Figure 1) [7,35,36]. The gene discussed is ATRX; the disease is alpha thalassemia-X-linked intellectual disability syndrome.