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 patients with milder clinical manifestations and no dependence on transfusion therapy, the term thalassemia intermedia is usually applied. Genetic mechanisms that may ameliorate the clinical expression of homozygous beta-thalassemia include coinheritance of alpha-thalassemia, inheritance of mild beta-globin gene mutations, and increased gamma-globin chain production, which may partially compensate for the lack of beta-globin 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, types of beta-thalassemia mutations, and the presence of a polymorphic site 5' to the G gamma-globin gene, which has been described as associated with increased gamma-globin chain production 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 thalassemia genotypes can provide information useful for prognosis and/or more appropriate management of homozygous beta-thalassemia patients. The results indicate that, in general, the major factor modifying the clinical 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 phenotype, the inheritance of two mild beta-thalassemia alleles results in almost all cases (11 of 12 cases in this study) in thalassemia intermedia phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)