Expression of the β thalassemia gene in the first trimester fetus

To determine whether β thalassemia can be detected in the fetus, blood was obtained from abortuses of normal mothers and of mothers with β thalassemia trait. The red cells were incubated with radioactive leucine and the globin chains were analyzed by radiochromatography. Two independent methods were utilized to correct the results for contamination by maternal radioactive β-chain, and the corrected β/γ ratios were compared to a previously established range of normal fetal β/γ synthetic ratios obtained by similar measurements in pure fetal cells. In the erythroid cells of 3 fetuses from mothers with β thalassemia trait, the β/γ synthetic ratio was normal in two. The 3rd had a β/γ ratio of 0.04 at 10 1/2 wk, a 50% reduction, consistent with fetal β thalassemia trait. Two other fetuses, derived from parents both of whom had β thalassemia trait, were also studied. One had a β/γ ratio of 0.029 at 8 wk, a 65% reduction, also consistent with β thalassemia trait. The cells of the other had a ratio of essentially zero at 11 wk, highly suggestive of homozygous β thalassemia. Although further experience will be needed to distinguish the homozygous and the heterozygous states reliably, it now appears that the β thalassemia gene is expressed in the first trimester. Therefore, these data suggest that the antenatal diagnosis of β thalassemia is becoming an attainable goal.