DETECTION OF THE (--(SEA)) DOUBLE ALPHA-GLOBIN GENE DETECTION BY A SIMPLE IMMUNOLOGICAL ASSAY FOR EMBRYONIC ZETA-GLOBIN CHAINS

Homozygous alpha-thalassemia alpha-thal-1!, with loss of all four alp ha-globin genes, causes lethal hydrops fetalis. The most common mutati on producing this syndrome is the Southeast Asian (--SEA) double alpha -globin gene deletion. Erythrocytes from adults heterozygous for the ( --SEA) deletion have minute amounts of embryonic zeta-globin chains de tectable by anti-zeta-globin monoclonal antibodies. Among 225 peripher al blood samples tested by a simple anti-zeta-immunobinding tetrazoliu m dye test, 81 were positive and 144 were negative. The majority of su bjects were of Filipino, Chinese, or Laotian ancestry. All 81 positive samples were confirmed by Bam HI digests and a zeta-cDNA probe to hav e the (--SEA) mutation. The (--SEA) double alpha-deletion was the only abnormality in 58. In the others, it was combined with alpha-globin o r beta-globin mutations, or coincidental iron deficiency. Four other s amples from (--SEA) heterozygotes were negative by this immunologic as say. Anti-zeta negative samples included 78 deletions of the total alp ha-globin region, (--Tot), 23 single alpha-globin deletions, and a var iety of beta-globin mutations; 16 normocytic samples with normal alpha -genes were also negative. Ten anti-zeta positive and 25 anti-zeta neg ative samples had benign triplicated zeta-globin genes. In this popula tion, the sensitivity of this test was 95%; and specificity for the (- -SEA) mutation was 100%. Anti-zeta immunobinding testing provides rapi d, simple, and reliable screening for the (--SEA ) double alpha-globin deletion, although it does not detect the (--Tot) total alpha-deletio nS. (C) 1993 Wiley-Liss, Inc.