Compound heterozygosity for a mild β⁺ and a rare β⁰-thalassemia allele

Hematological and hemoglobin composition data are presented for 14 members of a Surinam family (and for 1 unrelated subject) with either a β-thalassemia heterozygosity [5 with the -29 (A → G) β⁺ mutation and 5 with the IVS II-849 (A → G) β⁰ mutation] or a compound heterozygosity (the 5 remaining patients). Identification of the mutation was by hybridization of amplified DNA with ³²P-labelled synthetic oligonucleotides. The data indicate distinct differences between the two groups of heterozygotes, mainly in degree of microcytosis and hypochromia, in Hb A₂ level, and in the level of (G)γ (high in the -29 heterozygotes and low in the IVS II-849 heterozygotes). The 5 compound heterozygotes had a thalassemia intermedia with high Hb F levels (high (G)γ), elevated Hb A₂, and Hb A levels comparable to those seen in patients with a homozygosity for the -29 mutation or with the combination of this β⁺-thalassemia and Hb S. An α-thalassemia-2 heterozygosity (-3.7 kb deletion) was present in 2 patients. Their hematological data were improved over those for the patients with four α globin genes; one was the mother of two sets of twins. The high (G)γ value in the Hb F of the compound heterozygotes suggests that the high Hb F production in the condition is mainly directed by the chromosome with the -29 (A → G) mutation.