E. Kanavakis et al., MOLECULAR CHARACTERIZATION OF HOMOZYGOUS (HIGH HBA2) BETA-THALASSEMIA-INTERMEDIA IN GREECE, Pediatric hematology and oncology, 12(1), 1995, pp. 37-45
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.