Summary
A new type of hemoglobin F, in which isoleucine in position 75 (E 19) of the γ chain is replaced by a threonine residue, has been found in 29 out of 32 homozygotes for β thalassemia. The amount of this hemoglobin ranges from traces to 40% of the total Hb F. The same γ75 Thr chain is also present in the Hb F of 40% of normal newborns and premature infants examined, of one 14-week-old fetus and in one out of 3 patients with aplastic anemia and raised levels of Hb F. Our results strongly suggest that the synthesis of this new chain is under the control of a γ gene nonallelic with those coding for Aγ and Gγ chains.
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Bernini, L. F., Fiorelli, G., Matuonto, V., Bianchi, G., Chiesa, G.: Polimorfismo strutturale dell'emoglobina fetale umana. Atti riunioni gruppo per lo studio dell'eritrocita, p. 25. Milano: Cilab 1971
Betke, K., Marti, H. Q., Schlicht, I.: Estimation of small percentages of fetal hemoglobin. Nature (Lond.) 184, 1877–1879 (1959)
Cauchi, M. N., Clegg, J. B., Weatherall, D. J.: Haemoglobin F Malta: a new foetal haemoglobin variant with a high incidence in Maltese infants. Nature (Lond.) 223, 311–313 (1969)
Cimino, R., Ventruto, V.: Determinazione dell'Hb A2 in soggetti normali e microcitemici mediante elettroforesi su Cellogel. Progr. med. (Napoli) 23, 436–439 (1967)
Clegg, J. B., Naughton, W. A., Weatherall, D. J.: Abnormal human hemoglobin. Separation and characterization of the alpha and beta chains by chromatography, and the determination of two new variants, Hb Chesapeake and Hb J Bangkok. J. molec. Biol. 19, 91–108 (1966)
Dacie, J. V., Lewis, S. M.: Practical haematology, 4th ed. London: Churchill 1970
Dayhoff, M. O.: Atlas of protein sequence and structure. National biomedical research foundation Vo. 5 (1972)
Griffoni, V., Kamuzora, H., Lehmann, H., Charlesworth, D.: A new Hb F variant: F Sardinia γ 75 (E 19) isoleucine → threonine found in a family with Hb G Philadelphia, β chain deficiency and a Lepore-like haemoglobin, indistinguishable from Hb A2. Acta haemat. (Basel) 53, 347–355 (1975)
Huisman, T. H. J., Schroeder, W. A., Bannister, W. H., Grech, J. L.: Evidence for four nonallelic structural genes for the γ chain of human fetal hemoglobin. Biochem. Genet. 7, 131–139 (1972a)
Huisman, T. H. J., Schroeder, W. A., Efremov, G. D., Duma, H., Mladenovski, B., Hyman, C. B. Rachmilewitz, A. E., Bouver, N., Miller, A. B., Brodie, A., Shelton, J. R., Shelton, J. B., Apell, G.: The present status of the heterogeneity of fetal hemoglobin in β thalassemia: an attempt to unify some observations in thalassemia and related conditions. Ann. N.Y. Acad. Sci. 232, 107–124 (1974)
Huisman, T. H. J., Wrightstone, R. N., Wilson, J. B., Schroeder, W. A., Kendall, A. G.: Hemoglobin Kenya, the product of fusion of γ and β polypeptide chains. Arch. Biochem. Biophys. 153, 850–853 (1972b)
Jenkins, G. C., Beale, D., Black, A. J., Huntsman, R. G., Lehmann, H.: Hemoglobin F Texas I (α2γ2 5 Glu → Lys) a variant of haemoglobin F. Brit. J. Haemat. 13, 252–255 (1967)
Kamuzora, H., Ringelhann, B., Konotey-Ahulu, R. I. D., Lehmann, H., Lorkin, P. A.: Further investigations on the chain of a Ghanaian adult, homozygous for hereditary persistence of foetal haemoglobin: Isolation of γCB-3 fragment and determination of Gγ: Aγ ratio in human haemoglobins. Acta haemat. (Basel) 53, 315–320 (1975)
Kendall, A. G., Ojwang, P. J., Schroeder, W. A.: Hemoglobin Kenya, the product of γ-β fusion: Studies in the family. Amer. J. hum. Genet. 25, 548 (1973)
Schroeder, W. A., Huisman, T. H. J., Shelton, J. R., Shelton, J. B., Kleihauer, E. F., Dozy, A. M., Robertson, B.: Evidence for multiple structural genes for the γ chain of human fetal hemoglobin. Proc. nat. Acad. Sci. (Wash.) 60, 537–544 (1968)
Sick, K., Beale, D., Irvine, D., Lehmann, H., Goodall, P. T., McDougall, S.: Hemoglobin G Copenhagen and hemoglobin J Cambridge. Two new beta chain variants of hemoglobin A. Biochim. biophys. Acta (Amst.) 140, 231–242 (1967)
Weatherall, D. J., Cartner, R., Clegg, J. R., Wood, W. G., Macrae, I. A., Mackenzie, A.: A form of hereditary persistence of foetal haemoglobin characterised by uneven cellular distribution of haemoglobin F and production of haemoglobins A and A2 in homozygotes. Brit. J. Haemat. 29, 205–220 (1975)
Weatherall, D. J., Clegg, J. B.: Hereditary persistence of fetal haemoglobin. Brit. J. Haemat. 29, 191–198 (1975)
Wajcman, H., Labie, D., Schapira, G.: Haemoglobin Tours: Thr β-87 (F3) deleted and haemoglobin St. Antoine: Gly to Leu β74–75 (E 18–19) deleted. Consequences for oxygen affinity and protein stability. Biochim. biophys. Acta (Amst.) 295, 495–504 (1973)
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Ricco, G., Mazza, U., Turi, R.M. et al. Significance of a new type of human fetal hemoglobin carrying a replacement isoleucine → threonine at position 75 (E 19) of the γ chain. Hum Genet 32, 305–313 (1976). https://doi.org/10.1007/BF00295821
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DOI: https://doi.org/10.1007/BF00295821