Deletion of α-globin genes in haemoglobin-H disease demonstrates multiple α-globin structural loci

Abstract

FOUR clinical syndromes are associated with α thalassaemia: (1) the silent carrier state (α thalassaemia-2) with no clinical effect; (2) heterozygous α thalassaemia (α thalassaemia-1) in which a more severe defect in α-chain synthesis produces microcytic red cells but little or no anaemia; (3) haemoglobin-H disease usually the combination of α thalassaemia-1 and α thalassaemia-2 resulting in mild to moderate haemolytic anaemia and (4) hydrops fetalis associated with haemoglobin Barts an invariably fatal condition which represents the homozygous state of α thalassaemia-1 (for recent reviews see refs 1 and 2). To explain these syndromes one hypothesis proposes that α thalassaemia-1 and α thalassaemia-2 are caused by a defect of greater and lesser severity affecting alleles of a single α-globin locus³. A second hypothesis is based on evidence that the α-globin structural gene is duplicated⁴; the four syndromes may be the result of involvement of one, two, three or all four α structural genes by thalassaemia. In this study we tested these hypotheses by measuring the number of α-globin structural genes in haemoglobin-H disease and the results firmly support the latter hypothesis.