title: beta-Thalassaemia intermedia in a Turkish girl: homozygosity for G-->A substitution at +22 relative to the beta-globin cap site.
abstract: We provide the first description of a homozygote patient for the G-->A substitution in the 5' UTR of the beta-globin gene. The proband was a 17-year-old girl with beta-thalassaemia intermedia who had never received a blood transfusion. The physical examination revealed a well-developed women with no facial or bony abnormalities. There was mild paleness and mild splenomegaly which was 2 cm below the costal margin. The haemoglobin (Hb) was 7.6 g/dl, Hb A(2) 5.4% and Hb F 14.6% of the total Hb. The Hb A(2) of both parents was 3.5%. The Hb F level in the mother and father were 0.9, 1.2% and the mean cell volume (MCV) value was 70 and 72 fl respectively. DNA analysis of the beta-gene region of the propositus revealed homozygosity for a G-->A substitution at nucleotide +22 relative to the beta-gene cap site, within a functional downstream region that was referred to as the DCE (downstream core element). In addition to the data obtained previously from in vitro transcription assays, clinical findings and in vivo expression studies gave some valuable clues about the effect of +22 G-->A mutation on the expression of beta-gene. Phenotypic expression of this homozygous patient is highly suggestive that G-->A substitution at nt +22 confers a relatively mild (silent) beta(+)-thalassaemia phenotype.
authors.affiliation: Hacettepe University, Science Faculty, Department, of Molecular Biology, Beytepe, Ankara, Turkey. roner@hacettepe.edu.tr
authors.forename: R
authors.initials: R
authors.lastname: Oner
authors.forename: C
authors.initials: C
authors.lastname: Oner
authors.forename: E
authors.initials: E
authors.lastname: Birben
authors.forename: M
authors.initials: M
authors.lastname: Sözen
authors.forename: F
authors.initials: F
authors.lastname: Gümrük
authors.forename: A
authors.initials: A
authors.lastname: Gürgey
authors.forename: C
authors.initials: C
authors.lastname: Altay
mesh_terms: D020121:5' Untranslated Regions; D000293:Adolescent; D005260:Female; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D010641:Phenotype; D017354:Point Mutation; D014421:Turkey; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D005914:Globins