βB-Thalassaemia intermedia in a Turkish girl: Homozygosity for G→A substitution at +22 relative to the β-globin cap site

We provide the first description of a homozygote patient for the G→A substitution in the 5′ UTR of the β-globin gene. The proband was a 17-year-old girl with β-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 A₂ 5.4% and Hb F 14.6% of the total Hb. The Hb A₂ 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 β-gene region of the propositus revealed homozygosity for a G→A substitution at nucleotide +22 relative to the β-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 β-gene. Phenotypic expression of this homozygous patient is highly suggestive that G→A substitution at nt +22 confers a relatively mild (silent) β⁺-thalassaemia phenotype.