The molecular defect that has been demonstrated in alpha-thalassemia is the deletion of the alpha-globin structural genes. Since thalassemias are composed of heterogeneous groups of disorders, other types of defects could also result in alpha-thalassemia. We studied a Chinese family in which analysis of the mode of inheritance of alpha-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 alpha-globin mRNA sequences show that in addition to the usual deletion defect, a nondeletion defect produces the phenotype of alpha-thalassemia-1. The combination of the deletion and non-deletion defects results in hemoglobin-H disease and not homozygous alpha-thalassemia associated with hydrops fetalis.

DOI: 10.1056/NEJM197711172972002
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