Globin chain synthesis in the alpha thalassemia syndromes

Yuet Wai Kan; Elias Schwartz; David G. Nathan

doi:10.1172/JCI105933

Globin chain synthesis in the alpha thalassemia syndromes

Yuet Wai Kan, Elias Schwartz, and David G. Nathan

Published November 1, 1968 - More info

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Abstract

Whole blood samples of patients with various forms of alpha thalassemia including hemoglobin H disease, alpha thalassemia trait, and the “silent carrier” state were incubated with leucine-¹⁴C for definition of relative rates of production of alpha and beta chains in these disorders. The chains were separated by carboxymethyl cellulose chromatography in the presence of 8 M urea and dithiothreitol. Their absorptions at 280 mμ were determined and their radioactivities measured in a liquid scintillation spectrometer. After correction for differences in extinction coefficients, the specific activities of the widely separated alpha and beta peaks were determined. In 11 nonthalassemic individuals, the alpha/beta specific activity ratios were found to be 1.02±0.07; in nine patients with alpha thalassemia trait, 0.77±0.05; in six patients with hemoglobin H disease, 0.41±0.11; and in four “silent carriers,” 0.88 with a range of 0.82-0.95. The results show that in peripheral blood, alpha chain production relative to beta chain production is indeed limited in the alpha thalassemia syndromes. Hemoglobin H disease results from doubly heterozygous inheritance of a gene resulting in moderate depression of alpha chain production (alpha thalassemia trait) and a gene resulting in very mild depression of alpha chain production (the “silent carrier” syndrome.”