RNA transcripts of the beta-thalassaemia allele IVS-2-654 C-->T: a small amount of normally processed beta-globin mRNA is still produced from the mutant gene.

IVS-2-654 C-->T is a common Chinese beta-thalassaemia mutation. Previous studies report that this mutation resulted in the formation of an abnormally spliced mRNA and the absence of detectable normal beta-globin mRNA, hence the mutation was considered to cause beta o-thalassaemia. We recently used the method of PCR amplified cDNA copies of circulating erythroid cell mRNA to analyse the mutant gene transcripts and found that this IVS-2-654 mutation does not abolish normal RNA processing entirely, but that a significant amount (over 15%) of normally processed beta-globin mRNA is produced. Microglobin chain biosynthetic analysis using the HPLC method showed that beta-globin chain was also present in the blood of patients with IVS-2-654 C-->T mutation. Accordingly, this mutant allele leads to a beta (+)-thalassaemia. Further, the methodology described in this paper provides a new approach towards the detection of RNA transcripts of beta-thalassaemia alleles as well as the study of gene expression in beta-thalassaemia and other genetic diseases.