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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Palena, A Articles by Anagnou, N. Search for Related Content PubMed PubMed Citation Articles by Palena, A Articles by Anagnou, N. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Eastern European (delta beta) zero-thalassemia: molecular characterization of a novel 9.1-kb deletion resulting in high levels of fetal hemoglobin in the adult [see comments] A Palena, A Blau, G Stamatoyannopoulos and NP Anagnou Department of Basic Sciences, University of Crete School of Medicine, Heraklion, Greece. A novel deletion in the human beta-globin gene cluster associated with increased levels of fetal hemoglobin (HbF) in adult life was molecularly characterized in a member of a family of Eastern European descent. The phenotype of the deletion, documented in five members of the family, shows mild hypochromia and microcytosis (mean corpuscular Hb, 24 to 25.9 pg; mean corpuscular volume, 74 to 78.5 fL) but high production of HbF (13% to 24%) with heterocellular distribution (36% to 86% F cells). Extensive restriction enzyme mapping of the beta-globin cluster and sequencing of the region encompassing the breakpoints showed that the deletion starts 1,612 bp upstream of the cap site of the delta-globin gene, and terminates within the first intron of the beta-globin gene, deleting 9.1 kb of DNA. This length is definitely shorter than the average 12.0 kb of the previously characterized (delta beta) zero-thalassemias. The 5' breakpoint of the new deletion is close to that of the Yugoslavian delta beta-thalassemia deletion, whereas the 3' breakpoint is very close to those of the Turkish and the Greek beta zero-thalassemia deletions. The breakpoints of the deletion occur within a direct repeat containing a tetranucleotide exhibiting homology to a donor-splice site, and is symmetrically flanked by a set of 13- and 14-bp homologous complementary sequences, respectively. It is likely that the deletion may be the result of an "illegitimate" or "nonhomologous" recombination event to which these two short sequences may have contributed. It is of interest that the novel deletion (9.1 kb) is comparable to the Italian HPFH-5 deletion (12.9 kb), regarding both the size and the position of the breakpoints. However, the HPFH-5 deletion includes sequences flanking the breakpoints that are preserved in the new deletion. Considering the resulting two discrete phenotypes (ie, delta beta-thalassemia v HPFH), it can be hypothesized that the deleted sequences in the Italian HPFH-5 mutation may harbor regulatory elements that exert a negative control on the gamma-globin gene expression. Volume 83, Issue 12, pp. 3738-3745, 06/15/1994 Copyright © 1994 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. P. Anagnou, C. Perez-Stable, R. Gelinas, F. Costantini, K. Liapaki, M. Constantopoulou, T. Kosteas, N. K. Moschonas, and , and George Stamatoyannopoulos Sequences Located 3` to the Breakpoint of the Hereditary Persistence of Fetal Hemoglobin-3 Deletion Exhibit Enhancer Activity and Can Modify the Developmental Expression of the Human Fetal A[IMAGE]-Globin Gene in Transgenic Mice J. Biol. Chem., April 28, 1995; 270(17): 10256 - 10263. [Abstract] [Full Text] [PDF]

	Copyright © 1994 by American Society of Hematology         Online ISSN: 1528-0020