Suppression of the nonsense mutation in homozygous beta 0 thalassaemia

Nature. 1979 Oct 18;281(5732):602-3. doi: 10.1038/281602a0.


The common form of beta thalassaemia associated with elevated haemoglobin A2 levels can be broadly classified as beta + or beta 0 type according to the presence or absence of beta-globin chain synthesis in the homozygous state. The molecular pathology of each type is heterogeneous. Apart from a subgroup of Indo-Pakistani patients, the beta-globin structural gene is intact in the majority of patients with beta 0 thalassaemia. The amount of beta-globin mRNA present in the reticulocytes of these patients varies: in some it is absent or barely detectable; in others, a substantial amount is present, but it is nonfunctional. We recently demonstrated that the molecular lesion in a Chinese patient with nonfunctional beta-globin mRNA was due to the mutation of the normal lysine codon AAG at amino acid 17 to the amber terminator codon UAG, which prematurely terminates the beta-globin chain. In the present study we demonstrate the first example of a nonsense mutation in humans which can be suppressed in vitro by the suppressor tRNA, as has been found in other eukaryotic cells and viruses.

Publication types

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

MeSH terms

  • Codon
  • Genes
  • Mutation
  • RNA, Transfer / metabolism
  • Serine / genetics
  • Suppression, Genetic
  • Thalassemia / genetics*


  • Codon
  • Serine
  • RNA, Transfer