Identification of a Point Mutation in Position – 83 (G>A) of the β Globin Gene Promoter and the Influence of Globin Genes Mutation on the HbA2 Level

Carriers of typical β thalassemia alleles have microcytic hypochromic red blood cells with elevated Hb A2 values and a normal or slightly elevated level of Hb F. The increased level of Hb A2 is a reliable marker for heterozygous beta-thalassemia while Hb A2 levels within normal ranges do not exclude heterozygous beta-thalassemia. A male patient of Gabonese ancestry with both parents belonging to the Obamba sub-population was referred to us because of persistent microcytosis with anisopoikylocytosis and spherocytosis in the absence of clinical signs. The Hb separation pattern on alkaline electrophoresis and on ion exchange HPLC was normal. The Hb A2 level was 3.5% and the HbF level was 0.8%. Direct sequencing of the β globin genes revealed a G>A transition in position − 83 upstream of the cap site. The − 83 G>A substitution is located in a region between the CACCC motif (from − 90 to − 86) and the CCAAT motif (from − 76 to − 72) and has not been reported before. An alpha thalassemia associated with the β mutation was considered as well as a θ gene defect. Both hypotheses were based on the Hb A2 level.