caa a22 4500 467986614 CHVBK 20180323112533.0 cr unu---uuuuu 170328e19901201xx s 000 0 eng 10.1007/BF00197701 doi (NATIONALLICENCE)springer-10.1007/BF00197701 Intrinsic potential for high fetal hemoglobin production in a Druze family with β-thalassemia is due to an unlinked genetic determinant [Elektronische Daten] [Ariella Oppenheim, Avi Yaari, Deborah Rund, Eliezer Rachmilewitz, David Nathan, Corinne Wong, Haig Kazazian Jr., Barbara Miller] Summary: 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. Springer-Verlag, 1990 Oppenheim Ariella Department of Hematology, Hadassah University Hospital, 91120, Jerusalem, Israel aut Yaari Avi Department of Hematology, Hadassah University Hospital, 91120, Jerusalem, Israel aut Rund Deborah Department of Hematology, Hadassah University Hospital, 91120, Jerusalem, Israel aut Rachmilewitz Eliezer Department of Hematology, Hadassah University Hospital, 91120, Jerusalem, Israel aut Nathan David Children's Hospital Medical Center, 02115, Boston, MA, USA aut Wong Corinne The Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA aut Kazazian Jr. Haig The Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA aut Miller Barbara The Milton S. Hershey Medical Center, 17033, Hershey, PA, USA aut Human Genetics Springer-Verlag 86/2(1990-12-01), 175-180 0340-6717 86:2<175 1990 86 439 https://doi.org/10.1007/BF00197701 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00197701 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Oppenheim Ariella Department of Hematology, Hadassah University Hospital, 91120, Jerusalem, Israel aut NATIONALLICENCE 700 1- Yaari Avi Department of Hematology, Hadassah University Hospital, 91120, Jerusalem, Israel aut NATIONALLICENCE 700 1- Rund Deborah Department of Hematology, Hadassah University Hospital, 91120, Jerusalem, Israel aut NATIONALLICENCE 700 1- Rachmilewitz Eliezer Department of Hematology, Hadassah University Hospital, 91120, Jerusalem, Israel aut NATIONALLICENCE 700 1- Nathan David Children's Hospital Medical Center, 02115, Boston, MA, USA aut NATIONALLICENCE 700 1- Wong Corinne The Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Kazazian Jr Haig The Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Miller Barbara The Milton S. Hershey Medical Center, 17033, Hershey, PA, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 86/2(1990-12-01), 175-180 0340-6717 86:2<175 1990 86 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer