Abnormal hemoglobin anti-Lepore Hong Kong compound with β0-thalassemia ameliorate thalassemia severity when co-inherited with a-thalassemia

Abstract Background Abnormal hemoglobin anti-Lepore Hong Kong is rare βδ fusion variants resulted from non-homologous crossover during meiosis. Anti-Lepore Hong Kong always showed extraordinary increased HbA2. In this study, we used multiplex ligation-dependent probe amplification (MLPA) and single molecular real time (SMRT) sequencing, as well as Sanger sequencing, to detect variants in five unrelated families with abnormal increased HbA2 level. Results All the probands in these five families were detected with anti-Lepore Hong Kong heterozygotes. Among them, two families were compounded with β 0 -thalassemia and α-thalassemia (-- SEA / or α CS α/). The heterozygotes of anti-Lepore Hong Kong had an average 17.7% of HbA2 level and behaved normal. However, when compounded with β 0 -thalassemia and α-thalassemia, the probands had higher HbA2 level (30.2%-40.8%) and behaved with β-thalassemia trait. Moreover, the determination of α/β-mRNA ratio showed a slightly downregulation of β-globin, similar to that of β-thalassemia minor. Conclusions Our study first identifies the compound heterozygotes with anti-Lepore Hong Kong and β 0 -thalassemia and α-thalassemia, and provide better information in prenatal counseling.