Identification of a Nondeletion Defect in α-Thalassemia

Publisher Website
Google Scholar
Abstract
The molecular defect that has been demonstrated in α-thalassemia is the deletion of the α-globin structural genes. Since thalassemias are composed of heterogeneous groups of disorders, other types of defects could also result in α-thalassemia. We studied a Chinese family in which analysis of the mode of inheritance of α-thalassemia-1 and hemoglobin-H disease suggests a lesion that is not due to structural-gene deletion. Molecular hybridization studies with synthetic radioactive DNA's complementary to α-globin mRNA sequences show that in addition to the usual deletion defect, a nondeletion defect produces the phenotype of α-thalassemia-1. The combination of the deletion and nondeletion defects results in hemoglobin-H disease and not homozygous α-thalassemia associated with hydrops fetalis. (N Engl J Med 297:1081–1084, 1977)