Intrinsic potential for high fetal hemoglobin production in a Druze family with β-thalassemia is due to an unlinked genetic determinant

Ariella Oppenheim, Avi Yaari, Deborah Rund, Eliezer A. Rachmilewitz, David Nathan, Corinne Wong, Haig Kazazian, Barbara Miller

Research output: Contribution to journalArticle

Abstract

The mechanism for elevated production of fetal hemoglobin (Hb F) in a Druze patient with β°-thalassemia intermedia was investigated. Heterozygous family members exhibited normal Hb F levels, suggesting that the increase in γ-gene expression in the propositus may be partly due to anemic stress. Erythroid progenitors of these family members cultured in vitro [burst forming units (erythroid); (BFUe)] showed elevated synthesis of Hb F, indicating the existence of a genetically determined intrinsic capacity for high Hb F production in this family. The propositus was found to be homozygous for a IVS2-position 1 mutation, on the background of Mediterranean haplotype I, which is not known to be linked to high Hb F production. Moreover, extensive molecular studies of the β-globin gene cluster, including sequence analysis of the promoter regions of the γ-globin genes, did not reveal any cisacting mechanism that could account for the high Hb F production in the propositus. A young niece of the propositus with β°-thalassemia major was recently discovered, who was homozygous for the same β-globin allele and haplotype as the propositus. However, unlike her uncle, she does not have a high Hb F level and presents with a severe clinical course. Her inability to produce high Hb F suggests that the genetic determinant for increased γ-gene expression in the propositus is unlinked to the β-globin gene cluster.

Original languageEnglish (US)
Pages (from-to)175-180
Number of pages6
JournalHuman Genetics
Volume86
Issue number2
DOIs
StatePublished - 1990

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Fetal Hemoglobin
Thalassemia
Globins
beta-Thalassemia
Multigene Family
Haplotypes
Gene Expression
Erythroid Precursor Cells
Genetic Promoter Regions
Sequence Analysis
Alleles
Mutation
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Intrinsic potential for high fetal hemoglobin production in a Druze family with β-thalassemia is due to an unlinked genetic determinant. / Oppenheim, Ariella; Yaari, Avi; Rund, Deborah; Rachmilewitz, Eliezer A.; Nathan, David; Wong, Corinne; Kazazian, Haig; Miller, Barbara.

In: Human Genetics, Vol. 86, No. 2, 1990, p. 175-180.

Research output: Contribution to journalArticle

Oppenheim, Ariella ; Yaari, Avi ; Rund, Deborah ; Rachmilewitz, Eliezer A. ; Nathan, David ; Wong, Corinne ; Kazazian, Haig ; Miller, Barbara. / Intrinsic potential for high fetal hemoglobin production in a Druze family with β-thalassemia is due to an unlinked genetic determinant. In: Human Genetics. 1990 ; Vol. 86, No. 2. pp. 175-180.
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abstract = "The mechanism for elevated production of fetal hemoglobin (Hb F) in a Druze patient with β°-thalassemia intermedia was investigated. Heterozygous family members exhibited normal Hb F levels, suggesting that the increase in γ-gene expression in the propositus may be partly due to anemic stress. Erythroid progenitors of these family members cultured in vitro [burst forming units (erythroid); (BFUe)] showed elevated synthesis of Hb F, indicating the existence of a genetically determined intrinsic capacity for high Hb F production in this family. The propositus was found to be homozygous for a IVS2-position 1 mutation, on the background of Mediterranean haplotype I, which is not known to be linked to high Hb F production. Moreover, extensive molecular studies of the β-globin gene cluster, including sequence analysis of the promoter regions of the γ-globin genes, did not reveal any cisacting mechanism that could account for the high Hb F production in the propositus. A young niece of the propositus with β°-thalassemia major was recently discovered, who was homozygous for the same β-globin allele and haplotype as the propositus. However, unlike her uncle, she does not have a high Hb F level and presents with a severe clinical course. Her inability to produce high Hb F suggests that the genetic determinant for increased γ-gene expression in the propositus is unlinked to the β-globin gene cluster.",
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