RNA TRANSCRIPTS OF THE BETA-THALASSEMIA ALLELE IVS-2-654 C-]T - A SMALL AMOUNT OF NORMALLY PROCESSED BETA-GLOBIN MESSENGER-RNA IS STILL PRODUCED FROM THE MUTANT-GENE

IVS-2-654 C --> T is a common Chinese beta-thalassaemia mutation. Prev ious studies report that this mutation resulted in the formation of an abnormally spliced mRNA and the absence of detectable normal beta-glo bin mRNA, hence the mutation was considered to cause beta degrees-thal assaemia. 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 pr ocessing entirely, but that a significant amount (over 15%) of normall y processed beta-globin mRNA is produced. Microglobin chain biosynthet ic analysis using the HPLC method showed that beta-globin chain was al so present in the blood of patients with IVS-2-654 C --> T mutation. A ccordingly, this mutant allele leads to a beta(+)-thalassaemia. Furthe r, the methodology described in this paper provides a new approach tow ards the detection of RNA transcripts of beta-thalassaemia alleles as well as the study of gene expression in beta-thalassaemia and other ge netic diseases.