Detection of β-Thalassemia Carrier by Direct Analysis of β-Globin Gene Lesions

DNA was prepared from peripheral blood mononuclear cells of 114 Chinese with low erythrocyte mean corpuscular volume and analyzed by allele-specific DNA amplification for the presence of mutant alleles in the β-globin gene that account for about 90% of β-thalassemia in Chinese. A total of 9 mutations of the five most frequent mutant alleles were detected in 8 individuals. All mutant sequences were confirmed later by DNA sequencing. However, no mutation of these mutant alleles was detected in the remaining 106 individuals with low erythrocyte mean corpuscular volume including 22 who also had Hb A₂ content of 6.0% or more. Our results seem to suggest that the presence of β-thalassemia allele does not correlate very well with red blood cell indices and that direct DNA analysis by allele-specific DNA amplification is an accurate method to identify β-thalassemia heterozygotes.