SEARCH:   Advanced

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 Moi, P. Articles by Pirastu, M. Search for Related Content PubMed PubMed Citation Articles by Moi, P. Articles by Pirastu, M. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Delta-thalassemia due to a mutation in an erythroid-specific binding protein sequence 3' to the delta-globin gene P Moi, G Loudianos, J Lavinha, S Murru, P Cossu, R Casu, L Oggiano, M Longinotti, A Cao and M Pirastu Ospedale Regionale per le Microcitemie, USL 21, Cagliari, Italy. We have previously described a family of Northern Sardinian descent in which the propositus was affected by thalassemia major resulting from compound heterozygosity for codon 39 nonsense mutation and the beta +IVS II nt 745 mutation and in which all heterozygotes for the beta +IVS II nt 745 mutation had normal hemoglobin (Hb) A2 levels. To define the reasons for normal HbA2 levels in otherwise typical beta- thalassemia heterozygotes, we cloned and sequenced the delta- thalassemia gene in cis to the beta +IVS II nt 745 mutation. The sequence analysis showed a single nucleotide substitution (G----A) at position 69 nts (delta +69) downstream to the polyA addition site. Dot blot analysis with an oligonucleotide probe complementary to the delta +69 mutation detected this mutation in several heterozygotes for the beta +IVS II nt 745 mutation from the proband's family, but failed to show it either in a group of normal individuals of the same origin or in nonrelated heterozygotes for the beta +IVS II nt 745 mutation of the same or different descent from the proband. The delta +69 (G----A) mutation may be responsible for the low delta-globin output from the beta +IVS II nt 745 chromosome or could be a silent polymorphism not affecting the function of the delta-globin gene. The normal G at position 69 is part of a sequence very similar to the core DNA (A/T)GATA(A/G) motif (GATA box) that is a binding site for the GATA-1 protein. Gel-retardation assay has shown that a DNA fragment containing the GATA motif with the G----A at position +69 has increased binding affinity for erythroid-specific DNA binding protein(s) as compared with the wild-type sequence. These findings may suggest that the delta +69 mutation is responsible for the deficient function of the in cis delta- globin gene. Volume 79, Issue 2, pp. 512-516, 01/15/1992 Copyright © 1992 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: J. V. Ponomarenko, T. I. Merkulova, G. V. Vasiliev, Z. B. Levashova, G. V. Orlova, S. V. Lavryushev, O. N. Fokin, M. P. Ponomarenko, A. S. Frolov, and A. Sarai rSNP_Guide, a database system for analysis of transcription factor binding to target sequences: application to SNPs and site-directed mutations Nucleic Acids Res., January 1, 2001; 29(1): 312 - 316. [Abstract] [Full Text] [PDF] M. Ahmed, W. Taylor, P. R. Smith, and M. A. Becker Accelerated Transcription of PRPS1 in X-linked Overactivity of Normal Human Phosphoribosylpyrophosphate Synthetase J. Biol. Chem., March 12, 1999; 274(11): 7482 - 7488. [Abstract] [Full Text] [PDF]

	Copyright © 1992 by American Society of Hematology         Online ISSN: 1528-0020