Gene mapping of Malaysian alpha thalassemias with alpha and zeta globin gene probes

Restriction enzyme analysis of the alpha and zeta globin genes was carried out in four cases of Hb Bart's hydrops fetalis, in three patients with Hb H disease without Hb CoSp, in three patients with Hb H disease with Hb CoSp, in 47 individuals with alpha thalassemia trait, and in 47 normal individuals. All four cases of Hb Bart's hydrops fetalis resulted from deletions of alpha 1 and alpha 2 globin genes which did not extend to the psi zeta 1 and zeta 2 globin genes. The same type of deletion was observed in alpha thal1 carriers, but two newborns (one Malay and one of Chinese extraction) had a nondeletion type of alpha thal1 which was confirmed by quantitative alpha globin gene analysis. In addition, two other newborns diagnosed as alpha thal1 trait carriers (one Malay, one Chinese) were shown to have a deletion of both alpha globin genes by quantitative alpha globin gene analysis, but further testing with zeta globin gene probe failed to reveal an abnormal fragment length characteristic of an alpha globin gene deletion. We believe that this last condition is due to a large deletion which includes all alpha globin genes and all zeta globin genes on the same chromosome. On another front, Bgl II restriction analysis of all four Hb Bart's hydrops fetalis cases and the alpha thal1 trait carriers showed a 10.5-kb Bgl II restriction fragment, in the hydrops fetalis as a single band, while in the carriers this 10.5-kb fragment was accompanied by the usual normal 12.5-kb and 11.3-kb fragments. We report that this 10.5-kb fragment, previously thought to be specific for the Southeast Asian alpha thal1 gene deletion, is also common in normal individuals. Nevertheless, digestion with other enzymes can clearly differentiate the alpha thal1 and normal genotypes. We distinguish the findings in the alpha thalassemias from the extensive DNA polymorphism in the region of the alpha and zeta globin genes.