Mild Beta-Thalassemia intermedia Caused by Compound Heterozygosity for ^Gγ(^Aγδβ)^o/β-Thalassemia and Molecular Characterization of the Defect in Four Chinese Families

Abstract

Molecular characterization of the compound heterozygous condition – ^Gγ(^Aγδβ)^o/β-thalassemia – in four families showing mild β-thalassemia intermedia was carried out using DNA amplification techniques. Using the Amplification Refractory Mutation System (ARMS) to confirm the β-mutations and DNA amplification to detect the 100-kb Chinese-specific ^Gγ(^Aγδβ)^o-deletion, two families were confirmed to possess ^Gγ(^Aγδβ)^o/β-thalassemia with the IVSII No. 654 β⁺-allele. In the third family, the ^Gγ(^Aγδβ)^o-deletion was confirmed in the father and the mother was a β-thalassemia carrier with the cd 41–42 β^o-allele. Their affected child with ^Gγ(^Aγδβ)^o/β-thalassemia was found to be transfusion dependent. The same ^Gγ(^Aγδβ)^o-deletion and β-thalassemia (cd 41–42) was also confirmed in a fourth family. In addition, the mother was also diagnosed with Hb H disease (genotype -α^3.7/–^SEA). Both the children were found to possess ^Gγ(^Aγδβ)^o/β-thalassemia but they were not transfusion dependent and this could be due to co-inheritance of α-thalassemia-2 (genotype-α^3.7/αα) in the children together with their compound heterozygous condition.

Contrasting co-inheritance of alpha and beta mutations in delta beta thalassemia and hereditary persistence of fetal hemoglobin: a study from India

“…These patients had more propensity towards blood transfusion and higher splenomegaly [14,21]. Tan Jin Ai et al also reported double heterozygosity for δβ and β-thalassemia in four Chinese families [22]. Our results are quiet similar to above-mentioned studies [14,21,23].…”

The identification of beta-thalassemia mutants in Brazilians with high Hb F levels

“…21 This mutation creates a new splicing site which affects RNA processing. 24 Even though it is rare in Brazil (1.75%), the frequency of this mutation in the analyzed group shows the influence of Asiatic components in the formation of the Brazilian population.…”