Detection of a Hb A2-Melbourne (HBD: c.130G'A) combined with β-thalassemia in a Chinese individual

Abstract

Background: Thalassemia is common in Southeast Asian countries, including China. Hb A2-Melbourne is a rare hemoglobin variant and has never been reported in China. Here, we report a Hb A2-Melbourne combined with β-thalassemia in Chinese individuals which is the second case described in the published reports. Methods: Complete blood counts (CBC) of a 28-year-old female showed signs of thalassemia during a routine screening. Hemoglobin analysis was subsequently performed using capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC). Four common deletional α-thalassemia detection was carried out using a gap-polymerase chain reaction (PCR). PCR and reverse dot-blot were used to detect three non-deletional α-thalassemia and 17 types of point mutations in β-thalassemia. Finally, it was identified by Sanger sequencing. Her husband also had CBC, hemoglobin analysis, and genetic diagnosis. Results: CBC of the couple showed Hb 103 and 139 g/L, mean corpuscular volume 58 and 63.1 fL, mean corpuscular hemoglobin 19.7 and 20.4 pg, respectively. Hemoglobin analysis revealed Hb X 2.4%, Hb A2 2.8% by CE and Hb X 2.9%, Hb A2 2.4% by HPLC in the female. The results of her husband were Hb A93.5%, Hb A2 5.7%, Hb F 0.8% by CE. Genetic analysis of both spouses detected the same CD 41/42 mutations in β-globin gene. Sanger sequencing of female identified a mutation of the δ-globin gene (HBD:c.130G'A), corresponding to Hb A2-Melbourne. Conclusion: Hb A2-Melbourne can lead to misdiagnosis of β-thalassemia. δ-globin gene mutation must be carefully examined in routine thalassemia screening.