title: The G----A mutation at position +22 3' to the Cap site of the beta-globin gene as a possible cause for a beta-thalassemia.
abstract: We describe the occurrence of a chromosome with a G----A mutation at position +22 relative to the Cap site that was found in five patients with beta-thalassemia. All patients had a common type of beta-thalassemia mutation on the second chromosome, namely the frameshift at codon 8 (-AA), the IVS-I-110 (G----A) and the IVS-II-1 (G----A) mutations. The beta genes of two patients, including the 5' and 3' untranslated regions, were completely sequenced and no other mutations, except a few polymorphic sites, were observed. Dot-blot analyses failed to demonstrate this G----A mutation at +22 in nearly 400 beta-thalassemia chromosomes and 180 normal chromosomes. Heterozygotes have the features of a high Hb A2-beta-thalassemia heterozygosity, although the hematological parameters might be less abnormal than observed in heterozygotes for the more common beta-thalassemia mutations. The possibility has been presented suggesting that this mutation might impair the binding of mRNA to ribosomes. Another mutation in this segment of DNA, i.e. a C----G mutation at position +20, is observed exclusively on a chromosome which also carries the C----G mutation at IVS-II-745. It is postulated that the +20 C----G mutation accentuates the beta-thalassemia condition caused by the IVS-II-745 mutation; the mechanism might be similar to that suggested for the G----A at +22 mutation.
authors.affiliation: Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
authors.forename: R
authors.initials: R
authors.lastname: Oner
authors.forename: S
authors.initials: S
authors.lastname: Agarwal
authors.forename: A J
authors.initials: AJ
authors.lastname: Dimovski
authors.forename: G D
authors.initials: GD
authors.lastname: Efremov
authors.forename: G H
authors.initials: GH
authors.lastname: Petkov
authors.forename: C
authors.initials: C
authors.lastname: Altay
authors.forename: A
authors.initials: A
authors.lastname: Gurgey
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002031:Bulgaria; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis; D005914:Globins / Q000235:genetics*; D006115:Greece; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D012315:RNA Caps / Q000235:genetics; D013789:Thalassemia / Q000208:ethnology / Q000235:genetics*; D014421:Turkey
chemical_list: D012315:RNA Caps; D005914:Globins; D005319:Fetal Hemoglobin