Abnormal RNA processing due to the exon mutation of βE- globin gene

Stuart H. Orkin, Haig H. Kazazian, Stylianos E. Antonarakis, Harry Ostrer, Sabra C. Goff, Julianne P. Sexton

Research output: Contribution to journalArticlepeer-review

215 Scopus citations


As is typical of all β-thalassaemias1, the erythroid cells of individuals with the variant haemoglobin E (α2β 226Glu→Lys) exhibit a quantitative deficiency in their content of β-globin (in this case βE-globin) and its messenger RNA2,3. To determine the molecular basis of this phenotype, we have investigated the structure and expression of cloned βE-globin genes. We report here that the complete nucleotide sequence of a βE-gene revealed the expected GAG → AAG change in codon 26 but no other mutations. Expression of βE- globin genes introduced into HeLa cells revealed two abnormalities of RNA processing: Slow excision of intervening sequence-1 (IVS-1) and alternative splicing into exon-1 at a cryptic donor sequence within which the codon 26 nucleotide substitution resides. These results demonstrate a disturbance in the expression of the βE-gene attributable solely to the exon mutation - A novel mechanism for gene dysfunction.

Original languageEnglish (US)
Pages (from-to)768-769
Number of pages2
Issue number5894
StatePublished - Dec 1 1982

ASJC Scopus subject areas

  • General


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