Molecular characterization of Hb D-Punjab [beta 121(GH4)Glu -> Gln] in Thailand

We describe the hematological and DNA characterization of Hb D-Punjab [beta121(GH4)Glu --> Gln] in Thailand. Nine patients from five unrelated families were studied; four patients were simple carriers of Hb D-Punjab, two were compound heterozygotes for Hb D-Punjab/beta(+)-thalassemia; another two patients were double heterozygotes for Hb D-Punjab and alpha-thalassemia-2, and one patient was a compound heterozygote for Hb D-Punjab and Hb E [beta26(B8)Glu --> Lys]. Typical thalassemic indices with hypochromic microcytosis were observed in compound Hb D-Purjab/beta(+)-thalassemia and Hb D-Punjab/Hb E but normal hematological profiles were observed in the remaining cases. DNA sequencing of the beta-globin gene identified the GAA --> CAA substitution at codon 121 causing Hb D-Punjab in all. cases, and the -28 (A --> G) mutation for the beta(+)-thalassemia alleles. beta-Globin gene haplotype analysis demonstrated, for the first time, that all these Asian beta(D-Punjab) globin genes were associated with haplotype [-++-+++], previously undescribed in other populations. The finding of Hb D-Punjab in Thailand is compatible either with an independent origin of this abnormal hemoglobin or a spread of the Hb D-Punjab gene with a single origin among Asians.