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

Abstract

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 A2 or appearance of Hb A2-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, [δCD30(AGG>GGG) (n = 1)], 5 previously undescribed in Thailand, [δ-44(G>A) (n = 7), Hb A2-Troodos (n = 5), δIVSII-897(A>C) (n = 4), δ-68(C>T) (n = 2), and Hb A2-Indonesia (n = 1)], and 4 mutations previously found in Thailand, [Hb A2-Melbourne (n = 9), δ-77(T>C) (n = 3), Hb A2' (n = 1), and Hb A2-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 A2-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.

• Authors: Kritsada Singha, Goonnapa Fucharoen, Supan Fucharoen
• Journal: Annals of hematology (Ann Hematol) Vol. 100 Issue 8 Pg. 1953-1963 (Aug 2021) ISSN: 1432-0584 [Electronic] Germany
• PMID: 33834283 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• delta-Globins
• Hemoglobin A2

Topics

• Adolescent
• Adult
• Child
• Female
• Genetic Association Studies
• Hemoglobin A2 (genetics)
• Humans
• Male
• Mutation
• Thailand (epidemiology)
• Thalassemia (epidemiology, genetics)
• Young Adult
• delta-Globins (genetics)