Positional effect of cis/trans alpha globin gene deletions on the formation of "H" bodies

Normal individuals have four alpha-globin genes, two on each member of the chromosome 16 pair (alpha alpha/alpha alpha). The alpha-thalassemia trait phenotype associated with deletions of two alpha-genes can be either on the same chromosome, the cis type (alpha alpha/--), or on opposite chromosomes, the trans type (alpha-/alpha-). Traditionally, the observation on vitally stained smears of occasional cells containing "H" bodies has been used as an important diagnostic criterion for alpha-thalassemia trait. These "H" bodies are thought to be precipitated beta tetramers because of the presence of excess beta-globin chains. Our study in patients with various alpha-genotypes indicates that normal subjects (alpha alpha/alpha alpha) and patients with silent alpha-thalassemia trait (alpha alpha/alpha-) generally have no "H" bodies. However, patients with the two-gene deletion of the cis type alpha-thalassemia (alpha alpha/--) show the occasional "H" body, and those with Hb "H" disease (alpha-/-- or alpha cs-/--) show many such bodies. On the other hand, patients with two-gene deletion of the trans type (alpha-/alpha-) do not show "H" bodies. The number of "H" bodies found does not appear to correlate directly with the degree of imbalance in alpha- and beta-chain production among the various alpha-genotypes examined. The chemical nature of "H" bodies is discussed, and an alternative hypothesis that embryonic zeta chains expressed in the cis type but not in the trans type of alpha-thalassemia are involved in the formation of "H" bodies is proposed.