beta-Thalassaemia intermedia in a Turkish girl: homozygosity for G -> A substitution at+22 relative to the beta-globin cap site

We provide the first description of a homozygote patient for the G-->A subs titution 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 splenomeg aly which was 2 cin 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 paren ts 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 o f 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 t ranscription 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 s uggestive that G-A substitution at nt +22 confers a relatively mild (silent ) beta (+)-thalassaemia phenotype.