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

The δ-globin gene defects are clinically silent but interaction with β-thalassemia can lead to a misdiagnosis of β-thalassemia carrier. We report an extensive molecular characterization of δ-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 δ-globin gene defects. Of these 296 subjects, Hb and DNA analyses identified δ-hemoglobinopathies with 10 different mutations in 34 (0.11%) of them. These included a novel mutation, [δ ^{CD30(AGG>GGG)} (n = 1)], 5 previously undescribed in Thailand, [δ ^-44(G>A) (n = 7), Hb A ₂ -Troodos (n = 5), δ ^{IVSII-897(A>C)} (n = 4), δ ^-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), δ ^-77(T>C) (n = 3), Hb A ₂ ' (n = 1), and Hb A ₂ -Kiriwong (n = 1)]. Genetic heterogeneities seen included interactions of δ-globin gene defects with heterozygous Hb E, β-thalassemia, α-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 δ-globin gene mutations were developed. The results should prove useful to a prevention and control program of hemoglobinopathies in the region.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)