Summary
This symposium is concerned with recent studies that have attempted to define the molecular basis of the defects in globin synthesis which produce the hematologic manifestation of thalassemia. There have been two basic approaches to this problem. Analysis of the structure and synthesis of the various mutant globin chains in patients has permitted the formulation of a genetic hypothesis by which deletion of specific structural or regulator genes could produce the various forms the thalassemia. The second approach involves direct search for defects in the biochemical processes by which each structural gene directs the synthesis of a specific globin chain. The recent developments of these studies are reviewed and discussed briefly.
The thalassemia syndromes are a heterogeneous group of inherited hematologic disorders characterized by reduced or absent synthesis of the α-and non-α-globin chains, which form the apoprotein portion of hemoglobin. The cumulative results of all the various studies lead to the conclusion that the underlying basic genetic defect in the nucleus causes the decreased production of a globin chain-specific messenger RNA (mRNA), which in turn leads to a decreased amount of the globin chain, resulting in the unbalanced synthesis of globins. Thus, the major defects in the regulation of hemoglobin synthesis are transcriptional.
In α-thalassemia, α-chain specific mRNA is deficient because of gene deletion which has been demonstrated byin vitro synthesis of the complementary DNA(cDNA), followed by hybridization experiments to mRNA and DNA. On the basis of these studies, a gene deletion model may be proposed to explain the various forms of α-thalassemia and the heterogeneity of the population for the number of α-chain loci.
In β-thalassemia, the basic defects for the deficient β mRNA production remain to be clear. Although the cDNA-DNA hybridization experiments do not show actual β-chain gene deletion, a partial gene deletion including regulator genes that are predicted to be linked to the structural loci could be the basis of some cases of β- and δβ-thalassemias.
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Imamura, T. The molecular basis of the thalassemia syndromes. Jap J Human Genet 22, 113–128 (1977). https://doi.org/10.1007/BF01874278
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DOI: https://doi.org/10.1007/BF01874278