THE MOLECULAR-BASIS OF NORMAL HBA2 (TYPE-2) BETA-THALASSEMIA IN GREECE

Heterozygotes for beta-thalassemia usually have raised levels of HbA(2 ), but in Greece about 5% of beta-thalassemia carriers are observed to have normal or borderline levels. It is postulated that such cases ha ve mild beta(+) thalassemia mutations or coinheritance of delta-thalas semia. We selected 18 heterozygotes with the hematological phenotype o f normal HbA(2) (type 2) beta thalassemia who were negative for the de lta beta Corfu mutation, and screened them for previously defined Medi terranean beta-thalassemia and delta-thalassemia mutations. The coinhe ritance of beta and delta-thalassemia was demonstrated in four cases w ith the following genotypes: in cis beta(+) IVSII-n745/delta(+) 27, be ta(0)NS39/ delta(0)59(-A), beta(+)IVSI-n110/delta(0)59(-A) and in tran s beta(+)IVSI-n6 and delta(+)27. A further nine heterozygotes had mild beta(+)-thalassemia mutations (eight with the beta(+) IVSI-n6 mutatio n, one with the beta(+) polyA (A-->G) mutation). In four heterozygotes with severe beta-thalassemia chromosomes (2 beta(+)IVSI-n110, 1 beta( 0) FSC-6, 1 beta(0) IVSI-n1) no known delta-thalassemia mutations were observed. One case had a delta beta deletion chromosome. These result s indicate that the hematological phenotype of normal HbA(2) (type 2) beta-thalassemia in Greece is genetically heterogeneous; it is mainly associated with the delta beta Corfu mutation or coinheritance of beta and delta thalassemia mutations or with very mild beta(+)- thalassemi a mutations, mainly beta(+) IVSI-n6. In the rare cases with severe bet a-thalassemia mutations, the normal levels of HbA(2) may be due to coi nheritance of as yet undefined delta thalassemia mutations.