HbQ-Iran [α75 (EF4) Asp→His]/−α^3.7/β° IVSII.1 G→A in an Iranian Child: First Reported Case.

HbQ-Iran [α75 (EF4) Asp→His] is an α-chain variant first described in 1970, which substitution is not involved in the interchain contacts of hemoglobin. It has a slow-moving migration pattern on cellulose acetate at alkaline pH, that resembles the Hb S, but with normal solubility. The quantity of this variant in the heterozygous state has been reported to be 17–19%. Heterozygotes individuals with HbQ-Iran are hematologically asymptomatic and the combination with α⁺-thalassemia and β⁰- thalassemia has not been reported up to now.

We here described the hematological characteristics of a 5 years old child referred to the clinic of Kermanshah University. Physical examination revealed no enlargement of the spleen, and the initial blood count indicated a mild microcytic anemia with low levels of Hb (10g/dL), a hematocrit of 30.5% and low MCV and MCH (59.3fL and 19.6pg) respectively. DNA analysis revealed the presence of HbQ-Iran, −α^3.7 kb deletion of the alpha globin genes and also the presence of the mutation (IVSII.1.G→A) β⁰-thalassemia in the child. The study of the family revealed the presence of a minor β-thalassemia in the father and the HbQ-Iran in the mother. Both parents were heterozygous for the −α^3.7 deletion (−α^3.7/α α) in the α-globin genes. The coinheritance of HbQ-Iran with −α^3.7 deletion and β-thalassemia resulted in an elevation of the levels of HbQ-Iran to 22.4%. However, the remainder hematological values of the young patient indicated a significant reduction in MCV (59.3 fL) and MCH (19.6 pg), an elevation of HbF (6.3%) and of HbA₂ (3.7%) according to a picture of a minor β-thalassemia. This result demonstrated that HbQ-Iran is a benign structural variant, that in combination with β⁰-thalassemia and in the presence of a α⁺-thalassemia, produce a minor β-thalassemia picture with moderate anemia and elevation of HbF. The application of DNA technologies allowed the identification for the first time of the presence in one individual of three already known mutations, emphasizing the unique genetic heterogeneity of this population.