Homozygous or compound heterozygous state for β thalassemia

• Inheritance of mild β thalassemia alleles, β ‘silent’ and β⁺⁺, in homozygous or compound heterozygous states

  Phenotype depends on the sum total of β globin output

• Co-inheritance of α thalassemia

  Phenotype depends on severity of imbalance between α/non-α globin reflecting severity of α and β globin deficit

• Increased Hb F response

  • – Xmn1-^Gγ polymorphism

  • – β globin gene promoter mutations deletions or point mutations

  • – Trans-acting quantitative trait loci (QTLs) for Hb F on 6q, Xp, and 8q

Heterozygous state for β thalassemia

• Co-inheritance of extra α globin genes (ααα/αα, ααα/ααα, αααα/αα, αααα/αααα)

• Dominantly inherited β thalassemia (Hyperunstable β globin chain variants)

• Somatic deletion of the other β globin locus— mosaicism

Compound heterozygotes for β thalassemia and β chain variants
 e.g., Hb E/β thalassemia

Compound heterozygotes for β thalassaemia and HPFH or δβ thalassemia