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The levels of ζ, γ, and δ chains in patients with Hb H disease

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Summary

Details are given of a study of blood samples from 24 patients with Hb H disease from different Mediterranean countries and from the Far East. Four different types of α-thal-1 (--) were observed, namely-(α) (∼ 20.5-kb deletion);--MED-I (∼ 17.5-kb deletion);--MED-II (>26.5-kb deletion); and--SEA (∼ 18-kb deletion, in Orientals only). The α-thal-2 was mainly of the deletion type (16 with the 3.7-kb deletion; 1 with the 4.2-kb deletion), while 4 of the 7 patients with a nondeletional type had the five-nucleotide deletion at the donor splice site of the first intron of the α2 gene. All patients had a mild-to-moderate hemolytic anemia; no significant differences in hematology were observed between the groups. Hb A2 was decreased to about one-third of the normal level. The Hb H formation varied considerably and its quantitation was not always satisfactory. Patients with Hb H disease due to any α-thal-1 combined with a nondeletional α-thal-2 had the highest Hb H levels and a more marked anemia. The ζ chain production was small and absent in patients with the MED-II type of α-thal-1 because this deletion included the ζ and ψζ genes. The highest ζ chain levels were present in the four patients with the SEA type of α-thal-1. The γ chain production was increased, particularly in patients with a mutation of C → T at position-158 to the Gγ globin gene. This γ chain was primarily present as Hb Bart's (or γ4) and only about 15% was recovered as Hb F or α2γ2. The evaluation of the rate of γ chains produced in these patients was greatly facilitated by data from one patient who had Hb H disease and a heterozygosity for the Aγ-β+. The low levels of Hb A2 and of Hb F (relative to Hb Bart's) can be explained by a decreased affinity of α chains for δ and γ chains as compared with β chains in conditions of severe α chain deficiency.

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Medical College of Georgia, 30912-2100, Augusta, GA, USA

    Ferdane Kutlar, Jose M. Gonzalez-Redondo, Abdullah Kutlar & Titus H. J. Huisman

  2. Children's Medical Center, Hacettepe University, Ankara, Turkey

    Aytemiz Gurgey & Çigdem Altay

  3. Research Center for New Technologies, Macedonian Academy of Sciences and Arts, 91000, Skopje, Yugoslavia

    Georgi D. Efremov

  4. Children's Hospital, Oakland Research Institute, 94609, Oakland, CA, USA

    Klara Kleman

Authors
  1. Ferdane Kutlar
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  2. Jose M. Gonzalez-Redondo
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  3. Abdullah Kutlar
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  4. Aytemiz Gurgey
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  5. Çigdem Altay
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  6. Georgi D. Efremov
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  7. Klara Kleman
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  8. Titus H. J. Huisman
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Kutlar, F., Gonzalez-Redondo, J.M., Kutlar, A. et al. The levels of ζ, γ, and δ chains in patients with Hb H disease. Hum Genet 82, 179–186 (1989). https://doi.org/10.1007/BF00284054

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  • DOI: https://doi.org/10.1007/BF00284054

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