α-Thalassemia, Mental Retardation, and Myelodysplastic Syndrome

This article describes three rare syndromes in which the presence of alpha-thalassemia provided an important clue to the molecular basis of the underlying condition. It exemplifies how rare diseases allied with careful clinical observation can lead to important biological principles. Two of the syndromes, ATR-16 and ATR-X, are characterized by alpha-thalassemia in association with multiple developmental abnormalities including mental retardation. The third condition, ATMDS, is an acquired disorder in which alpha-thalassemia arises in the context of myelodysplasia. Intriguingly, mutations in the chromatin remodeling factor, ATRX, are common to both ATR-X syndrome and ATMDS.