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Your search keyword '"Higgs DR"' showing total 15 results
Start Over Author "Higgs DR" Publisher american society of hematology
15 results on '"Higgs DR"'

14. Potential new approaches to the management of the Hb Bart's hydrops fetalis syndrome: the most severe form of α-thalassemia.

Author

King AJ and Higgs DR

Subjects
Humans, Blood Transfusion, Intrauterine, Hemoglobins, Abnormal genetics, Hemoglobins, Abnormal metabolism, Hydrops Fetalis diagnosis, Hydrops Fetalis genetics, Hydrops Fetalis metabolism, Hydrops Fetalis therapy, Perinatal Care methods, alpha-Thalassemia diagnosis, alpha-Thalassemia genetics, alpha-Thalassemia metabolism, alpha-Thalassemia therapy
Abstract

The α-thalassemia trait, associated with deletions removing both α-globin genes from 1 chromosome (genotype ζ αα/ζ--), is common throughout Southeast Asia. Consequently, many pregnancies in couples of Southeast Asian origin carry a 1 in 4 risk of producing a fetus inheriting no functional α-globin genes (ζ--/ζ--), leading to hemoglobin (Hb) Bart's hydrops fetalis syndrome (BHFS). Expression of the embryonic α-globin genes (ζ-globin) is normally limited to the early stages of primitive erythropoiesis, and so when the ζ-globin genes are silenced, at ∼6 weeks of gestation, there should be no α-like globin chains to pair with the fetal γ-globin chains of Hb, which consequently form nonfunctional tetramers (γ 4 ) known as Hb Bart's. When deletions leave the ζ-globin gene intact, a low level of ζ-globin gene expression continues in definitive erythroid cells, producing small amounts of Hb Portland (ζ 2 γ 2 ), a functional form of Hb that allows the fetus to survive up to the second or third trimester. Untreated, all affected individuals die at these stages of development. Prevention is therefore of paramount importance. With improvements in early diagnosis, intrauterine transfusion, and advanced perinatal care, there are now a small number of individuals with BHFS who have survived, with variable outcomes. A deeper understanding of the mechanism underlying the switch from ζ- to α-globin expression could enable persistence or reactivation of embryonic globin synthesis in definitive cells, thereby providing new therapeutic options for such patients., Competing Interests: Conflict-of-interest disclosure: The authors declare no competing financial interests., (© 2018 by The American Society of Hematology. All rights reserved.)

Published
2018
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15. Gene regulation in hematopoiesis: new lessons from thalassemia.

Author

Higgs DR

Subjects
Animals, Globins biosynthesis, Hematopoiesis physiology, Humans, Multigene Family genetics, Multigene Family physiology, Mutation, Thalassemia physiopathology, Transcriptional Activation physiology, Globins genetics, Hematopoiesis genetics, Thalassemia genetics, Transcriptional Activation genetics
Abstract

Over the past fifty years, many advances in our understanding of the general principles controlling gene expression during hematopoiesis have come from studying the synthesis of hemoglobin. Discovering how the alpha and beta globin genes are normally regulated and documenting the effects of inherited mutations which cause thalassemia have played a major role in establishing our current understanding of how genes are switched on or off in hematopoietic cells. Previously, nearly all mutations causing thalassemia have been found in or around the globin loci, but rare inherited and acquired trans-acting mutations are being found with increasing frequency. Such mutations have demonstrated new mechanisms underlying human genetic disease. Furthermore, they are revealing new pathways in the regulation of globin gene expression which, in turn, may eventually open up new avenues for improving the management of patients with common types of thalassemia.

Published
2004
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