Identification of a nondeletion defect in alpha-thalassemia

N Engl J Med. 1977 Nov 17;297(20):1081-4. doi: 10.1056/NEJM197711172972002.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Deletion*
  • Female
  • Genes
  • Globins / biosynthesis
  • Hemoglobin H*
  • Hemoglobins, Abnormal*
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Nucleic Acid Hybridization
  • Pedigree
  • Phenotype
  • RNA, Messenger
  • Thalassemia / blood
  • Thalassemia / genetics*


  • Hemoglobins, Abnormal
  • RNA, Messenger
  • Globins
  • Hemoglobin H