DNA data have been collected for 41 patients with
beta-thalassemia intermedia without transfusion dependency. They belonged to 33 families, and 45 of their parents were included in the study. Eight patients were homozygous for the frameshift at
codon 8 (-AA), and nine were homozygous for the IVS-2 nt 1 (G----A) mutation; haplotypes IV and III, respectively, were associated with these mutations. Three patients had a G
gamma A gamma(delta beta)0-thalassemia homozygosity, characterized by a deletion of 13 kb. Of the remaining subjects, ten had a homozygosity for the IVS-1 nt 6 (T----C) mutation, and five were compound heterozygotes for one mild and one severe
thalassemia determinant. Combinations with
Hb Knossos, the T----A mutation at nt -30, the C----T mutation at nt -101, the G----A and G----C mutations at IVS-1 nt 5, and the G----A mutation at IVS-1 nt 110 were the other
thalassemia determinants resulting in
beta-thalassemia intermedia in the six remaining patients. Haplotypes IV and IX were associated with the latter three mutations. The C----T mutation at nt -158 5' to the G gamma gene was characteristic for haplotypes III, IV, and IX. Genotype and phenotype correlation indicated significant differences in some of the hematological parameters among patients with the frameshift at
codon 8 (-AA) or with the IVS-2 nt 1 (G----A) mutation, with both the frameshift at
codon 8 and the T----C mutation at IVS-1 nt 6, and with both the IVS-2 nt 1 (G----A) and IVS-1 nt 6 (T----C) mutations. Statistically significant differences were found in the mean values for
hemoglobin (
Hb) A2 in heterozygotes with the frameshift at
codon 8 (-AA) and the IVS-1 nt 5 (G----A) mutation. Variations in the number of
alpha-globin genes resulted in modifications of the phenotypical expression of the
beta-thalassemia intermedia determinants.