Molecular characterization and origins of Hb Constant Spring and Hb Paksé in Southeast Asian populations.

Hemoglobin Constant Spring (Hb CS) and Hb Paksé, two abnormal Hbs characterized by elongated alpha-globin chains resulting from mutations of the termination codon in the alpha2-globin gene, are the most prevalent nondeletional alpha-thalassemias in Southeast Asia. To determine the origins of these two variants in the region, we have determined alpha-globin gene haplotypes associated with these two variants on 120 Thai, eight Cambodian, and six Laos alleles, and the results were compared with those reported previously for the Chinese and Mediterranean. Five haplotypes were found to be associated with 131 alpha(CS) genes examined, whereas a single haplotype was linked to all the alpha(Paksé) genes in these Southeast Asian populations. All the alpha(CS) haplotypes differed from those of the Mediterranean, but one of them was similar to a Chinese alpha(CS) gene reported previously. It is concluded that there are multiple origins of the alpha(CS) and a single origin of the alpha(Paksé) mutations in Southeast Asia. Hematological findings confirm the mild thalassemia intermedia phenotypes for pure homozygous Hb CS and homozygous Hb CS with Hb E heterozygote and Hb E homozygote. The appearance of Hb CS peak by high-performance liquid chromatography analysis indicates the ability to form a tetrameric Hb molecule between the alpha(CS) and beta(E) chains, leading to a novel derivative with similar characteristics to Hb CS.