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.