MOLECULAR CHARACTERIZATION OF HOMOZYGOUS (HIGH HBA2) BETA-THALASSEMIA-INTERMEDIA IN GREECE

Homozygous beta-thalassemia is usually characterized by severe anemia requiring regular blood transfusion for survival. For homozygous patie nts with milder clinical manifestations and no dependence on transfusi on therapy, the term thalassemia intermedia is usually applied. Geneti c mechanisms that may ameliorate the clinical expression of homozygous beta-thalassemia include coinheritance of alpha-thalassemia, inherita nce of mild beta-globin gene mutations, and increased gamma-globin cha in production, which may partially compensate for the lack of beta-glo bin chain synthesis. To identify which of these factors may contribute to the modification of childhood homozygous, high-hemoglobin A2 (HbA2 ) beta-thalassemia in Greece, the interaction of alpha-thalassemia, ty pes of beta-thalassemia mutations, and the presence of a polymorphic s ite 5' to the G(gamma)-globin gene, which has been described as associ ated with increased gamma-globin chain production of similar studies i n 150 randomly in some cases, was assessed. The results were analyzed in light of similar studies in 150 randomly selected, homozygous, high -HbA2 beta-thalassemia patients with the aim of assessing whether thal assemia genotypes can provide information useful for prognosis and/or more appropriate management of homozygous beta-thalassemia patients. T he results indicate that, in general, the major factor modifying the c linical expression of homozygous, high-HbA2 beta-thalassemia in Greece is the inheritance of mild beta-thalassemia mutations. Although there is not always a complete correlation of genotype with clinical phenot ype, the inheritance of two mild beta-thalassemia alleles results in a lmost all cases (11 of 12 cases in this study) in thalassemia intermed ia phenotype. Therefore, the characterization of beta-globin gene muta tions may be useful in some cases for evaluation of prognosis and/or p rescription of treatment in Greek thalassemia intermedia children.