δ-Hemoglobinopathies in Thailand: screening, molecular basis, genotype-phenotype interaction, and implication for prevention and control of thalassemia

The delta-globin gene defects are clinically silent but interaction with beta-thalassemia can lead to a misdiagnosis of beta-thalassemia carrier. We report an extensive molecular characterization of delta-hemoglobinopathies in Thailand. Study was done on 32,108 subjects, encountered at the thalassemia screening. Six different approaches based on the reduced Hb A(2) or appearance of Hb A(2)-derivative were established for selective recruitment of subjects. Among 32,108 subjects, a total of 296 subjects were suspected of having delta-globin gene defects. Of these 296 subjects, Hb and DNA analyses identified delta-hemoglobinopathies with 10 different mutations in 34 (0.11%) of them. These included a novel mutation, [delta(CD30(AGG>GGG)) (n = 1)], 5 previously undescribed in Thailand, [delta(-44(G>A)) (n = 7), Hb A(2)-Troodos (n = 5), delta(IVSII-897(A>C)) (n = 4), delta(-68(C>T)) (n = 2), and Hb A(2)-Indonesia (n = 1)], and 4 mutations previously found in Thailand, [Hb A(2)-Melbourne (n = 9), delta(-77(T>C)) (n = 3), Hb A(2)' (n = 1), and Hb A(2)-Kiriwong (n = 1)]. Genetic heterogeneities seen included interactions of delta-globin gene defects with heterozygous Hb E, beta-thalassemia, alpha-thalassemia, and in cis locations of the Hb A(2)-Troodos and Hb E mutations found for the first time. Rapid identification methods of these delta-globin gene mutations were developed. The results should prove useful to a prevention and control program of hemoglobinopathies in the region.

Automated summary

This study conducted extensive molecular characterization of delta-hemoglobinopathies in Thailand, identifying 10 different mutations and developing rapid identification methods. The results provide valuable information for a prevention and control program of hemoglobinopathies in the region.