Журнал болезней крови и переливания крови

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Delta-Globin Gene Mutations Complicate the Diagnosis of β-Thalassemia

Hassan S, Ahmad R, Esa E, Yusoff YM, Yasin NM, Sahid ENM, Aziz NA, Hamid FSA, Omar SL, Bidin MB, Hamid AH, Zakaria z and Mokhri NM

Increased Hemoglobin A2 (HbA2) levels are used as invaluable markers for the detection of beta-thalassemia (β-thalassemia) carriers. However, a concomitant delta-globin gene (HBD) mutation reduces the HbA2 level resulting in the confusion of the β-thalassemia status.

Objectives: We sought to identify HBD mutations leading to low HbA2 level β-thalassemia carriers receiving the molecular diagnosis at the Institute for Medical Research (IMR), Malaysia.

Methods: Thirty-seven β-thalassemia carriers were ruled out of alpha-thalassemia (α-thalassemia) and underwent HBD genotyping by Sanger sequencing.

Results: Twenty-two β-thalassemia carriers with HBD mutations were identified. The most common mutations were HbA2-Indonesia and HbA2-Deventer. The HbA2-Deventer was found in ethnics from Sabah. Two new δ-globin mutations, Cap +48 (A>T) and HbA2-Shah Alam were identified among the Malays. Altogether, we identified seven δ-globin gene mutations. Relying upon HbA2 levels for β-thalassemia carrier status prediction is risky. A misdiagnosis could occur when β-thalassemia carrier interacts with delta-thalassemia (δ-thalassemia) lacking additional HbA2 fraction, leading to normal or borderline HbA2. Family screening and ethnicity are important to facilitate the accurate diagnosis of complicated cases.

Conclusions: Since δ-thalassemia modifies HbA2 levels, diagnosing borderline HbA2 β-thalassemia among Malaysians is vital. HBD mutations are heterogeneous and its deoxyribonucleic acid (DNA) analysis is important in our multi-ethnic populations.