Intrinsic potential for high fetal hemoglobin production in a Druze family with β-thalassemia is due to an unlinked genetic determinant
✍ Scribed by Ariella Oppenheim; Avi Yaari; Deborah Rund; Eliezer A. Rachmilewitz; David Nathan; Corinne Wong; Haig H. Kazazian; Barbara Miller
- Book ID
- 104659788
- Publisher
- Springer
- Year
- 1990
- Tongue
- English
- Weight
- 856 KB
- Volume
- 86
- Category
- Article
- ISSN
- 0340-6717
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✦ Synopsis
The mechanism for elevated production of fetal hemoglobin (Hb F) in a Druze patient with 13~assemia intermedia was investigated. Heterozygous family members exhibited normal Hb F levels, suggesting that the increase in 7-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 13-globin gene cluster, including sequence analysis of the promoter regions of the 7-globin genes, did not reveal any cis-acting mechanism that could account for the high Hb F production in the propositus. A young niece of the propositus with ~~ semia major was recently discovered, who was homozygous for the same 13-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 7-gene expression in the propositus is unlinked to the 13-globin gene cluster.