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

Ferdane Kutlar, Jose M. Gonzalez-Redondo, Abdullah Kutlar, Aytemiz Gurgey, Çigdem Altay, Georgi D. Efremov, Klara Kleman, Titus H.J. Huisman

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)179-186
Number of pages8
JournalHuman Genetics
Volume82
Issue number2
DOIs
StatePublished - May 1 1989

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RNA Splice Sites
Globins
Far East
Hemolytic Anemia
Gene Deletion
Hematology
Introns
Genes
Anemia
Nucleotides
Mutation
hemoglobin A2'
hemoglobin Bart's

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Kutlar, F., Gonzalez-Redondo, J. M., Kutlar, A., Gurgey, A., Altay, Ç., Efremov, G. D., ... Huisman, T. H. J. (1989). The levels of ζ, γ, and δ chains in patients with Hb H disease. Human Genetics, 82(2), 179-186. https://doi.org/10.1007/BF00284054

The levels of ζ, γ, and δ chains in patients with Hb H disease. / Kutlar, Ferdane; Gonzalez-Redondo, Jose M.; Kutlar, Abdullah; Gurgey, Aytemiz; Altay, Çigdem; Efremov, Georgi D.; Kleman, Klara; Huisman, Titus H.J.

In: Human Genetics, Vol. 82, No. 2, 01.05.1989, p. 179-186.

Research output: Contribution to journalArticle

Kutlar, F, Gonzalez-Redondo, JM, Kutlar, A, Gurgey, A, Altay, Ç, Efremov, GD, Kleman, K & Huisman, THJ 1989, 'The levels of ζ, γ, and δ chains in patients with Hb H disease', Human Genetics, vol. 82, no. 2, pp. 179-186. https://doi.org/10.1007/BF00284054
Kutlar F, Gonzalez-Redondo JM, Kutlar A, Gurgey A, Altay Ç, Efremov GD et al. The levels of ζ, γ, and δ chains in patients with Hb H disease. Human Genetics. 1989 May 1;82(2):179-186. https://doi.org/10.1007/BF00284054
Kutlar, Ferdane ; Gonzalez-Redondo, Jose M. ; Kutlar, Abdullah ; Gurgey, Aytemiz ; Altay, Çigdem ; Efremov, Georgi D. ; Kleman, Klara ; Huisman, Titus H.J. / The levels of ζ, γ, and δ chains in patients with Hb H disease. In: Human Genetics. 1989 ; Vol. 82, No. 2. pp. 179-186.
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abstract = "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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