δ-Hemoglobinopathies in Thailand: screening, molecular basis, genotype-phenotype interaction, and implication for
Kritsada Singha1,2, Goonnapa Fucharoen1, Supan Fucharoen3
1Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.
Insights
Molecular characterization of delta-hemoglobinopathies in Thailand identified 10 mutations, including novel variants, in 34 individuals. These findings aid in preventing hemoglobinopathies and avoiding misdiagnosis of beta-thalassemia carriers.
Area of Science:
- Genetics
- Molecular Biology
- Hematology
Background:
- Delta-globin gene defects are clinically silent but can be misdiagnosed as beta-thalassemia carriers.
- Molecular characterization of delta-hemoglobinopathies is crucial for accurate diagnosis and genetic counseling.
Purpose of the Study:
- To conduct an extensive molecular characterization of delta-hemoglobinopathies in Thailand.
- To identify and report novel and previously described delta-globin gene mutations and their interactions.
Main Methods:
- Screening of 32,108 subjects for hemoglobin abnormalities.
- Utilizing six different approaches for selective recruitment based on Hb A2 levels.
- Employing Hemoglobin (Hb) and DNA analyses for mutation identification.
Main Results:
- Identified 10 different delta-hemoglobinopathy mutations in 34 subjects (0.11%).
- Discovered one novel mutation (δCD30(AGG>GGG)) and five mutations previously undescribed in Thailand.
- Characterized interactions with Hb E, beta-thalassemia, and alpha-thalassemia, including a novel cis-location of Hb A2-Troodos and Hb E mutations.
Conclusions:
- Developed rapid identification methods for delta-globin gene mutations.
- The findings are valuable for hemoglobinopathy prevention and control programs in the region.
- Accurate identification of delta-hemoglobinopathies is essential to prevent misdiagnosis of beta-thalassemia carriers.
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.
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