New amber mutation in a β-thalassemic gene with nonmeasurable levels of mutant messenger RNA in vivo

G. F. Atweh, H. E. Brickner, X. X. Zhu, H. H. Kazazian, B. G. Forget

Research output: Contribution to journalArticlepeer-review

Abstract

We have identified a β-thalassemia gene that carries a novel nonsense mutation in a Chinese patient. This mutation, a G to T substitution at the first position of codon 43, changes the glutamic acid coding triplet (GAG) to a terminator codon (TAG). Based on oligonucleotide hybridization studies of 78 Chinese and Southeast Asian β-thalassemia chromosomes, we estimate that this mutation accounts for a small minority of the β-thalassemia mutations in that population. Study of the expression of this cloned gene in a transient expression system demonstrated a 65% decrease in levels of normally spliced mutant β-globin mRNA. However, the study of reticulocyte RNA isolated from an individual heterozygous for this mutation demonstrated a total absence of this mutant mRNA in vivo. The basis for this big discrepancy between the level of accumulated mRNA in vivo and in vitro is probably the result of differences in the stabilities of the mutant mRNA in erythroid cells.

Original languageEnglish (US)
Pages (from-to)557-561
Number of pages5
JournalJournal of Clinical Investigation
Volume82
Issue number2
DOIs
StatePublished - 1988

ASJC Scopus subject areas

  • Medicine(all)

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