title: A C----G mutation at nt position 6 3' to the terminating codon may be the cause of a silent beta-thalassemia.
abstract: We describe the hematological and clinical data for a young Greek patient with beta-thalassemia intermedia and for several members of her family. The patient had inherited the common IVS-I-1 (G----A) mutation from her mother, while the second beta-globin gene had a C----G mutation at position 6 3' to the terminating codon (term. + 6). Her father and three additional relatives with a heterozygosity for this newly discovered mutation had no hematological abnormalities, normal Hb A2 values, and a nearly normal in vitro chain synthesis ratio. Analyses of nearly 500 additional beta-thalassemia and normal chromosomes failed to detect this mutation which eliminates it as a common polymorphism. Although our findings may indicate a rare polymorphism, the probability that it represents the cause of diminished beta chain synthesis is very high indeed. We suggest that the C----G mutation in this untranslated region of the beta-globin gene causes a slight decrease in the stability of the mRNA which becomes clinically important only in situations when beta chain synthesis in trans is eliminated.
authors.affiliation: Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
authors.forename: L
authors.initials: L
authors.lastname: Jankovic
authors.forename: A J
authors.initials: AJ
authors.lastname: Dimovski
authors.forename: P
authors.initials: P
authors.lastname: Kollia
authors.forename: M
authors.initials: M
authors.lastname: Karageorga
authors.forename: D
authors.initials: D
authors.lastname: Loukopoulos
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D001483:Base Sequence; D001803:Blood Transfusion; D003062:Codon; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D006443:Hemoglobin A2 / Q000032:analysis; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D013156:Splenectomy; D013789:Thalassemia / Q000235:genetics* / Q000601:surgery / Q000628:therapy
chemical_list: D003062:Codon; D005914:Globins; D006443:Hemoglobin A2