Δ-globin Chain Research Articles

δ+-Thalassemia in Sardinia

AbstractWe have defined a new type of δ-thalassemia in which δ-globin chain synthesis is incompletely suppressed. Homozygotes have unusually low HbA2 levels, and double heterozygosity for this δ-thalassemia gene and β-thalassemia normalizes the HbA2 level. The δ-thalassemia occurs on a chromosome that is identifiable using polymorphic restriction endonuclease sites. We call this condition δ+-thalassemia, to distinguish it from the previously described δ0-thalassemia syndromes in which no δ-globin chain synthesis occurs.

Partial deletion of the α-globin structural gene in human α-thalassaemia

Defective synthesis of specific polypeptide chains of haemoglobins is the hallmark of human disorders known collectively as the thalassaemia syndromes1. Genetic lesions intimately linked to or within the globin genes are responsible for these conditions. Recently, the molecular basis of several forms of thalassaemia has been clarified by examination of the organization and structure of globin genes. Gene mapping studies using the gel blotting technique of Southern2 have revealed an array of deletions involving globin structural genes in thalassaemias3–12 and nucleotide sequencing has identified a point mutation responsible for thalassaemia in one individual13. In most α-thalassaemias, deletion of entire α-globin structural genes has been observed3,4. In specific forms of β-thalassaemia in which δ-globin chain expression is affected (δβ-thalassaemia, γδβ-thalassaemia and hereditary persistance of fetal haemoglobin syndrome), various deletions within the cluster of closely linked γ-, δ- and β-globin genes occur5–9. In some Asian Indian individuals with β°-thalassaemia, an internal deletion in the DNA involving the 3′-portion of the β-globin gene has been described10–12. Lastly, in one Chinese patient with β°-thalassaemia, a nonsense mutation within the β-sequence has been identified13. We now report a new genetic lesion present in some individuals with α-thalassaemia: an extensive deletion of the 5′ portion of the α-globin structural gene. This defect has been characterized by DNA sequence analysis of cloned α-thalassaemia genes.