Prenatal diagnosis of beta-thalassemia by reverse dot-blot hybridization in southern China

Beta-thalassemia (thal) is the most common genetic disease and is widely distributed in southern China. Prenatal diagnosis is needed to prevent the birth of thalassemic offspring in couples at-risk. This can be performed in the first or second trimester of pregnancy by DNA analysis using polymerase chain reaction (PCR). As there are more than 30 mutations causing beta-thal in Chinese, the point mutation detection by reverse dot-blot for common mutations together with direct DNA sequencing was developed for prenatal diagnosis. Using reverse dot-blot, we were able to offer complete diagnosis in 315 (99.4%) of 317 pregnancies. Only two fetuses needed the DNA sequencing technique for diagnosis. Of the 319 at-risk fetuses, 82 (25.7%) were found to be normal, 143 (44.8%) to be heterozygous for beta-thal and 94 (29.5%) to be affected with beta-thal. Therefore, the combination of reverse dot-blot with direct DNA sequencing can perform prenatal diagnosis by DNA analysis in almost all cases at- risk of beta-thal in southern China.